Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants
Identifieur interne : 000148 ( Pmc/Curation ); précédent : 000147; suivant : 000149Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants
Auteurs : Reiko Kagawa [Japon] ; Ryoji Fujiki [Japon] ; Miyuki Tsumura [Japon] ; Sonoko Sakata [Japon] ; Shiho Nishimura [Japon] ; Yuval Itan [États-Unis] ; Xiao-Fei Kong [États-Unis] ; Zenichiro Kato [Japon] ; Hidenori Ohnishi [Japon] ; Osamu Hirata [Japon] ; Satoshi Saito [Japon] ; Maiko Ikeda [Japon] ; Jamila El Baghdadi [Maroc] ; Aziz Bousfiha [Maroc] ; Kaori Fujiwara [Japon] ; Matias Oleastro [Argentine] ; Judith Yancoski [Argentine] ; Laura Perez [Argentine] ; Silvia Danielian [Argentine] ; Fatima Ailal [Maroc] ; Hidetoshi Takada [Japon] ; Toshiro Hara [Japon] ; Anne Puel [États-Unis, France] ; Stéphanie Boisson-Dupuis [États-Unis, France] ; Jacinta Bustamante [États-Unis, France] ; Jean-Laurent Casanova [États-Unis, France] ; Osamu Ohara [Japon] ; Satoshi Okada [Japon, États-Unis] ; Masao Kobayashi [Japon]Source :
- The Journal of allergy and clinical immunology [ 0091-6749 ] ; 2016.
Abstract
Germline heterozygous mutations in human
Estimate variations in CCD/DBD of STAT1
Mutagenized 342 individual wild-type amino acids in CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity.
Of these 342 mutants, 201 were neutral, 30 LOF, and 111 GOF in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the impact of two hypomorphic and dominant-negative mutations, E157K and G250E, in CCD of STAT1 that we found in two unrelated MSMD patients.
Systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and impact of heterozygous missense mutations in
Url:
DOI: 10.1016/j.jaci.2016.09.035
PubMed: 28011069
PubMed Central: 5471135
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000148
Links to Exploration step
PMC:5471135Curation
No country items
Aziz Bousfiha<affiliation><nlm:aff id="A8">Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</nlm:aff><wicri:noCountry code="subfield">Marocco</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca</wicri:regionArea></affiliation><affiliation><nlm:aff id="A8">Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</nlm:aff><wicri:noCountry code="subfield">Marocco</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca</wicri:regionArea></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants</title><author><name sortKey="Kagawa, Reiko" sort="Kagawa, Reiko" uniqKey="Kagawa R" first="Reiko" last="Kagawa">Reiko Kagawa</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Fujiki, Ryoji" sort="Fujiki, Ryoji" uniqKey="Fujiki R" first="Ryoji" last="Fujiki">Ryoji Fujiki</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Technology Development, Kazusa DNA Research Institute, Chiba</wicri:regionArea></affiliation></author><author><name sortKey="Tsumura, Miyuki" sort="Tsumura, Miyuki" uniqKey="Tsumura M" first="Miyuki" last="Tsumura">Miyuki Tsumura</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Sakata, Sonoko" sort="Sakata, Sonoko" uniqKey="Sakata S" first="Sonoko" last="Sakata">Sonoko Sakata</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Nishimura, Shiho" sort="Nishimura, Shiho" uniqKey="Nishimura S" first="Shiho" last="Nishimura">Shiho Nishimura</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Itan, Yuval" sort="Itan, Yuval" uniqKey="Itan Y" first="Yuval" last="Itan">Yuval Itan</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation></author><author><name sortKey="Kong, Xiao Fei" sort="Kong, Xiao Fei" uniqKey="Kong X" first="Xiao-Fei" last="Kong">Xiao-Fei Kong</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation></author><author><name sortKey="Kato, Zenichiro" sort="Kato, Zenichiro" uniqKey="Kato Z" first="Zenichiro" last="Kato">Zenichiro Kato</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Structural Medicine, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Structural Medicine, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu</wicri:regionArea></affiliation></author><author><name sortKey="Ohnishi, Hidenori" sort="Ohnishi, Hidenori" uniqKey="Ohnishi H" first="Hidenori" last="Ohnishi">Hidenori Ohnishi</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu</wicri:regionArea></affiliation></author><author><name sortKey="Hirata, Osamu" sort="Hirata, Osamu" uniqKey="Hirata O" first="Osamu" last="Hirata">Osamu Hirata</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Saito, Satoshi" sort="Saito, Satoshi" uniqKey="Saito S" first="Satoshi" last="Saito">Satoshi Saito</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Ikeda, Maiko" sort="Ikeda, Maiko" uniqKey="Ikeda M" first="Maiko" last="Ikeda">Maiko Ikeda</name><affiliation wicri:level="1"><nlm:aff id="A6">Department of Pediatrics, Okazaki City Hospital, Aichi, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Okazaki City Hospital, Aichi</wicri:regionArea></affiliation></author><author><name sortKey="El Baghdadi, Jamila" sort="El Baghdadi, Jamila" uniqKey="El Baghdadi J" first="Jamila" last="El Baghdadi">Jamila El Baghdadi</name><affiliation wicri:level="1"><nlm:aff id="A7">Genetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Genetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat</wicri:regionArea></affiliation></author><author><name sortKey="Bousfiha, Aziz" sort="Bousfiha, Aziz" uniqKey="Bousfiha A" first="Aziz" last="Bousfiha">Aziz Bousfiha</name><affiliation><nlm:aff id="A8">Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</nlm:aff><wicri:noCountry code="subfield">Marocco</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca</wicri:regionArea></affiliation></author><author><name sortKey="Fujiwara, Kaori" sort="Fujiwara, Kaori" uniqKey="Fujiwara K" first="Kaori" last="Fujiwara">Kaori Fujiwara</name><affiliation wicri:level="1"><nlm:aff id="A10">Department of Pediatrics, National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, National Hospital Organization Fukuyama Medical Center, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Oleastro, Matias" sort="Oleastro, Matias" uniqKey="Oleastro M" first="Matias" last="Oleastro">Matias Oleastro</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Yancoski, Judith" sort="Yancoski, Judith" uniqKey="Yancoski J" first="Judith" last="Yancoski">Judith Yancoski</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Perez, Laura" sort="Perez, Laura" uniqKey="Perez L" first="Laura" last="Perez">Laura Perez</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Danielian, Silvia" sort="Danielian, Silvia" uniqKey="Danielian S" first="Silvia" last="Danielian">Silvia Danielian</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Ailal, Fatima" sort="Ailal, Fatima" uniqKey="Ailal F" first="Fatima" last="Ailal">Fatima Ailal</name><affiliation><nlm:aff id="A8">Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</nlm:aff><wicri:noCountry code="subfield">Marocco</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca</wicri:regionArea></affiliation></author><author><name sortKey="Takada, Hidetoshi" sort="Takada, Hidetoshi" uniqKey="Takada H" first="Hidetoshi" last="Takada">Hidetoshi Takada</name><affiliation wicri:level="1"><nlm:aff id="A12">Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka</wicri:regionArea></affiliation></author><author><name sortKey="Hara, Toshiro" sort="Hara, Toshiro" uniqKey="Hara T" first="Toshiro" last="Hara">Toshiro Hara</name><affiliation wicri:level="1"><nlm:aff id="A12">Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka</wicri:regionArea></affiliation></author><author><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A15">Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A17">Howard Hughes Medical Institute, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Howard Hughes Medical Institute, New York, NY</wicri:regionArea></affiliation></author><author><name sortKey="Ohara, Osamu" sort="Ohara, Osamu" uniqKey="Ohara O" first="Osamu" last="Ohara">Osamu Ohara</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Technology Development, Kazusa DNA Research Institute, Chiba</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A18">Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea></affiliation></author><author><name sortKey="Okada, Satoshi" sort="Okada, Satoshi" uniqKey="Okada S" first="Satoshi" last="Okada">Satoshi Okada</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation></author><author><name sortKey="Kobayashi, Masao" sort="Kobayashi, Masao" uniqKey="Kobayashi M" first="Masao" last="Kobayashi">Masao Kobayashi</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28011069</idno><idno type="pmc">5471135</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471135</idno><idno type="RBID">PMC:5471135</idno><idno type="doi">10.1016/j.jaci.2016.09.035</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000148</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000148</idno><idno type="wicri:Area/Pmc/Curation">000148</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000148</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants</title><author><name sortKey="Kagawa, Reiko" sort="Kagawa, Reiko" uniqKey="Kagawa R" first="Reiko" last="Kagawa">Reiko Kagawa</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Fujiki, Ryoji" sort="Fujiki, Ryoji" uniqKey="Fujiki R" first="Ryoji" last="Fujiki">Ryoji Fujiki</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Technology Development, Kazusa DNA Research Institute, Chiba</wicri:regionArea></affiliation></author><author><name sortKey="Tsumura, Miyuki" sort="Tsumura, Miyuki" uniqKey="Tsumura M" first="Miyuki" last="Tsumura">Miyuki Tsumura</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Sakata, Sonoko" sort="Sakata, Sonoko" uniqKey="Sakata S" first="Sonoko" last="Sakata">Sonoko Sakata</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Nishimura, Shiho" sort="Nishimura, Shiho" uniqKey="Nishimura S" first="Shiho" last="Nishimura">Shiho Nishimura</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Itan, Yuval" sort="Itan, Yuval" uniqKey="Itan Y" first="Yuval" last="Itan">Yuval Itan</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation></author><author><name sortKey="Kong, Xiao Fei" sort="Kong, Xiao Fei" uniqKey="Kong X" first="Xiao-Fei" last="Kong">Xiao-Fei Kong</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation></author><author><name sortKey="Kato, Zenichiro" sort="Kato, Zenichiro" uniqKey="Kato Z" first="Zenichiro" last="Kato">Zenichiro Kato</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A5">Structural Medicine, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Structural Medicine, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu</wicri:regionArea></affiliation></author><author><name sortKey="Ohnishi, Hidenori" sort="Ohnishi, Hidenori" uniqKey="Ohnishi H" first="Hidenori" last="Ohnishi">Hidenori Ohnishi</name><affiliation wicri:level="1"><nlm:aff id="A4">Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu</wicri:regionArea></affiliation></author><author><name sortKey="Hirata, Osamu" sort="Hirata, Osamu" uniqKey="Hirata O" first="Osamu" last="Hirata">Osamu Hirata</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Saito, Satoshi" sort="Saito, Satoshi" uniqKey="Saito S" first="Satoshi" last="Saito">Satoshi Saito</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Ikeda, Maiko" sort="Ikeda, Maiko" uniqKey="Ikeda M" first="Maiko" last="Ikeda">Maiko Ikeda</name><affiliation wicri:level="1"><nlm:aff id="A6">Department of Pediatrics, Okazaki City Hospital, Aichi, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Okazaki City Hospital, Aichi</wicri:regionArea></affiliation></author><author><name sortKey="El Baghdadi, Jamila" sort="El Baghdadi, Jamila" uniqKey="El Baghdadi J" first="Jamila" last="El Baghdadi">Jamila El Baghdadi</name><affiliation wicri:level="1"><nlm:aff id="A7">Genetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Genetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat</wicri:regionArea></affiliation></author><author><name sortKey="Bousfiha, Aziz" sort="Bousfiha, Aziz" uniqKey="Bousfiha A" first="Aziz" last="Bousfiha">Aziz Bousfiha</name><affiliation><nlm:aff id="A8">Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</nlm:aff><wicri:noCountry code="subfield">Marocco</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca</wicri:regionArea></affiliation></author><author><name sortKey="Fujiwara, Kaori" sort="Fujiwara, Kaori" uniqKey="Fujiwara K" first="Kaori" last="Fujiwara">Kaori Fujiwara</name><affiliation wicri:level="1"><nlm:aff id="A10">Department of Pediatrics, National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, National Hospital Organization Fukuyama Medical Center, Hiroshima</wicri:regionArea></affiliation></author><author><name sortKey="Oleastro, Matias" sort="Oleastro, Matias" uniqKey="Oleastro M" first="Matias" last="Oleastro">Matias Oleastro</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Yancoski, Judith" sort="Yancoski, Judith" uniqKey="Yancoski J" first="Judith" last="Yancoski">Judith Yancoski</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Perez, Laura" sort="Perez, Laura" uniqKey="Perez L" first="Laura" last="Perez">Laura Perez</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Danielian, Silvia" sort="Danielian, Silvia" uniqKey="Danielian S" first="Silvia" last="Danielian">Silvia Danielian</name><affiliation wicri:level="1"><nlm:aff id="A11">Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires</wicri:regionArea></affiliation></author><author><name sortKey="Ailal, Fatima" sort="Ailal, Fatima" uniqKey="Ailal F" first="Fatima" last="Ailal">Fatima Ailal</name><affiliation><nlm:aff id="A8">Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</nlm:aff><wicri:noCountry code="subfield">Marocco</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="A9">Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</nlm:aff><country xml:lang="fr">Maroc</country><wicri:regionArea>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca</wicri:regionArea></affiliation></author><author><name sortKey="Takada, Hidetoshi" sort="Takada, Hidetoshi" uniqKey="Takada H" first="Hidetoshi" last="Takada">Hidetoshi Takada</name><affiliation wicri:level="1"><nlm:aff id="A12">Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka</wicri:regionArea></affiliation></author><author><name sortKey="Hara, Toshiro" sort="Hara, Toshiro" uniqKey="Hara T" first="Toshiro" last="Hara">Toshiro Hara</name><affiliation wicri:level="1"><nlm:aff id="A12">Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka</wicri:regionArea></affiliation></author><author><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A15">Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A14">Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A16">Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A17">Howard Hughes Medical Institute, New York, NY, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Howard Hughes Medical Institute, New York, NY</wicri:regionArea></affiliation></author><author><name sortKey="Ohara, Osamu" sort="Ohara, Osamu" uniqKey="Ohara O" first="Osamu" last="Ohara">Osamu Ohara</name><affiliation wicri:level="1"><nlm:aff id="A2">Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Technology Development, Kazusa DNA Research Institute, Chiba</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A18">Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama</wicri:regionArea></affiliation></author><author><name sortKey="Okada, Satoshi" sort="Okada, Satoshi" uniqKey="Okada S" first="Satoshi" last="Okada">Satoshi Okada</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="A3">St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y</wicri:regionArea></affiliation></author><author><name sortKey="Kobayashi, Masao" sort="Kobayashi, Masao" uniqKey="Kobayashi M" first="Masao" last="Kobayashi">Masao Kobayashi</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima</wicri:regionArea></affiliation></author></analytic><series><title level="j">The Journal of allergy and clinical immunology</title><idno type="ISSN">0091-6749</idno><idno type="eISSN">1097-6825</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P2">Germline heterozygous mutations in human <italic>STAT1</italic> can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases (MSMD), or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis (CMC). LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil and DNA-binding domains (CCD/DBD). Moreover, 6% of CMC patients with a GOF <italic>STAT1</italic> mutation develop mycobacterial disease, obscuring the functional significance of the identified <italic>STAT1</italic> mutations. Current computational approaches, such as <italic>combined annotation-dependent depletion</italic>, do not distinguish LOF and GOF variants</p></sec><sec id="S2"><title>Objective</title><p id="P3">Estimate variations in CCD/DBD of STAT1</p></sec><sec id="S3"><title>Method</title><p id="P4">Mutagenized 342 individual wild-type amino acids in CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity.</p></sec><sec id="S4"><title>Results</title><p id="P5">Of these 342 mutants, 201 were neutral, 30 LOF, and 111 GOF in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the impact of two hypomorphic and dominant-negative mutations, E157K and G250E, in CCD of STAT1 that we found in two unrelated MSMD patients.</p></sec><sec id="S5"><title>Conclusion</title><p id="P6">Systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and impact of heterozygous missense mutations in <italic>STAT1</italic> identified in patients with severe infectious diseases, including mycobacterial and fungal diseases.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">1275002</journal-id><journal-id journal-id-type="pubmed-jr-id">4431</journal-id><journal-id journal-id-type="nlm-ta">J Allergy Clin Immunol</journal-id><journal-id journal-id-type="iso-abbrev">J. Allergy Clin. Immunol.</journal-id><journal-title-group><journal-title>The Journal of allergy and clinical immunology</journal-title></journal-title-group><issn pub-type="ppub">0091-6749</issn><issn pub-type="epub">1097-6825</issn></journal-meta><article-meta><article-id pub-id-type="pmid">28011069</article-id><article-id pub-id-type="pmc">5471135</article-id><article-id pub-id-type="doi">10.1016/j.jaci.2016.09.035</article-id><article-id pub-id-type="manuscript">NIHMS841900</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kagawa</surname><given-names>Reiko</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">a</xref><xref ref-type="author-notes" rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Fujiki</surname><given-names>Ryoji</given-names></name><xref ref-type="aff" rid="A2">b</xref><xref ref-type="author-notes" rid="FN1">*</xref></contrib><contrib contrib-type="author"><name><surname>Tsumura</surname><given-names>Miyuki</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Sakata</surname><given-names>Sonoko</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Nishimura</surname><given-names>Shiho</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Itan</surname><given-names>Yuval</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Kong</surname><given-names>Xiao-Fei</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Kato</surname><given-names>Zenichiro</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A4">d</xref><xref ref-type="aff" rid="A5">e</xref></contrib><contrib contrib-type="author"><name><surname>Ohnishi</surname><given-names>Hidenori</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A4">d</xref></contrib><contrib contrib-type="author"><name><surname>Hirata</surname><given-names>Osamu</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Saito</surname><given-names>Satoshi</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib><contrib contrib-type="author"><name><surname>Ikeda</surname><given-names>Maiko</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A6">f</xref></contrib><contrib contrib-type="author"><name><surname>El Baghdadi</surname><given-names>Jamila</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A7">g</xref></contrib><contrib contrib-type="author"><name><surname>Bousfiha</surname><given-names>Aziz</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A8">h</xref><xref ref-type="aff" rid="A9">i</xref></contrib><contrib contrib-type="author"><name><surname>Fujiwara</surname><given-names>Kaori</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A10">j</xref></contrib><contrib contrib-type="author"><name><surname>Oleastro</surname><given-names>Matias</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A11">k</xref></contrib><contrib contrib-type="author"><name><surname>Yancoski</surname><given-names>Judith</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A11">k</xref></contrib><contrib contrib-type="author"><name><surname>Perez</surname><given-names>Laura</given-names></name><degrees>BSc</degrees><xref ref-type="aff" rid="A11">k</xref></contrib><contrib contrib-type="author"><name><surname>Danielian</surname><given-names>Silvia</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A11">k</xref></contrib><contrib contrib-type="author"><name><surname>Ailal</surname><given-names>Fatima</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A8">h</xref><xref ref-type="aff" rid="A9">i</xref></contrib><contrib contrib-type="author"><name><surname>Takada</surname><given-names>Hidetoshi</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A12">l</xref></contrib><contrib contrib-type="author"><name><surname>Hara</surname><given-names>Toshiro</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A12">l</xref></contrib><contrib contrib-type="author"><name><surname>Puel</surname><given-names>Anne</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">c</xref><xref ref-type="aff" rid="A13">m</xref><xref ref-type="aff" rid="A14">n</xref></contrib><contrib contrib-type="author"><name><surname>Boisson-Dupuis</surname><given-names>Stéphanie</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">c</xref><xref ref-type="aff" rid="A13">m</xref><xref ref-type="aff" rid="A14">n</xref></contrib><contrib contrib-type="author"><name><surname>Bustamante</surname><given-names>Jacinta</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A3">c</xref><xref ref-type="aff" rid="A13">m</xref><xref ref-type="aff" rid="A14">n</xref><xref ref-type="aff" rid="A15">o</xref></contrib><contrib contrib-type="author"><name><surname>Casanova</surname><given-names>Jean-Laurent</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A3">c</xref><xref ref-type="aff" rid="A13">m</xref><xref ref-type="aff" rid="A14">n</xref><xref ref-type="aff" rid="A16">p</xref><xref ref-type="aff" rid="A17">q</xref></contrib><contrib contrib-type="author"><name><surname>Ohara</surname><given-names>Osamu</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">b</xref><xref ref-type="aff" rid="A18">r</xref></contrib><contrib contrib-type="author"><name><surname>Okada</surname><given-names>Satoshi</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">a</xref><xref ref-type="aff" rid="A3">c</xref></contrib><contrib contrib-type="author"><name><surname>Kobayashi</surname><given-names>Masao</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">a</xref></contrib></contrib-group><aff id="A1"><label>a</label>Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, Hiroshima, Japan</aff><aff id="A2"><label>b</label>Department of Technology Development, Kazusa DNA Research Institute, Chiba, Japan</aff><aff id="A3"><label>c</label>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, N Y, USA</aff><aff id="A4"><label>d</label>Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan</aff><aff id="A5"><label>e</label>Structural Medicine, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan</aff><aff id="A6"><label>f</label>Department of Pediatrics, Okazaki City Hospital, Aichi, Japan</aff><aff id="A7"><label>g</label>Genetics Unit, Military Hospital Mohamed V, Hay Riad, 10100 Rabat, Morocco</aff><aff id="A8"><label>h</label>Laboratory of Clinical Immunology, Inflammation and Allergy, Faculty of Medicine and Pharmacy, Hassan II University of Casablanca, B.P 5696, Casablanca, Marocco</aff><aff id="A9"><label>i</label>Clinical Immunology Unit, Department of Pediatric Infectious Diseases, Averroes University Hospital, B.P 2698, Casablanca, Morocco</aff><aff id="A10"><label>j</label>Department of Pediatrics, National Hospital Organization Fukuyama Medical Center, Hiroshima, Japan</aff><aff id="A11"><label>k</label>Department of Immunology, “Juan Pedro Garrahan” National Hospital of Pediatrics, Buenos Aires, Argentina</aff><aff id="A12"><label>l</label>Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</aff><aff id="A13"><label>m</label>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</aff><aff id="A14"><label>n</label>Paris Descartes University, Sorbonne Paris Cité, Imagine Institute, Paris, France</aff><aff id="A15"><label>o</label>Center for the Study of Primary Immunodeficiencies, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France</aff><aff id="A16"><label>p</label>Pediatric Hematology-Immunology Unit, Assistance Publique-Hôpitaux de Paris, Necker Hospital for Sick Children, Paris, France</aff><aff id="A17"><label>q</label>Howard Hughes Medical Institute, New York, NY, USA</aff><aff id="A18"><label>r</label>Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan</aff><author-notes><corresp id="cor1">Correspondence: Satoshi Okada, MD, PhD, Department of Pediatrics, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan Tel: +81-82-257-5212 Fax: +81-82-257-5214 <email>saok969@gmail.com</email></corresp><fn id="FN1" fn-type="equal"><label>*</label><p id="P1">These authors contributed equally to this work</p></fn><fn fn-type="COI-statement" id="FN4"><p id="P28"><bold>Disclosure of potential conflict of interest:</bold></p><p id="P29">The authors have no conflict of interest to declare.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>12</day><month>1</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>20</day><month>12</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>7</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>7</month><year>2018</year></pub-date><volume>140</volume><issue>1</issue><fpage>232</fpage><lpage>241</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.jaci.2016.09.035</pmc-comment>
<abstract id="Abs1"><sec id="S1"><title>Background</title><p id="P2">Germline heterozygous mutations in human <italic>STAT1</italic> can cause loss of function (LOF), as in patients with Mendelian susceptibility to mycobacterial diseases (MSMD), or gain of function (GOF), as in patients with chronic mucocutaneous candidiasis (CMC). LOF and GOF mutations are equally rare and can affect the same domains of STAT1, especially the coiled-coil and DNA-binding domains (CCD/DBD). Moreover, 6% of CMC patients with a GOF <italic>STAT1</italic> mutation develop mycobacterial disease, obscuring the functional significance of the identified <italic>STAT1</italic> mutations. Current computational approaches, such as <italic>combined annotation-dependent depletion</italic>, do not distinguish LOF and GOF variants</p></sec><sec id="S2"><title>Objective</title><p id="P3">Estimate variations in CCD/DBD of STAT1</p></sec><sec id="S3"><title>Method</title><p id="P4">Mutagenized 342 individual wild-type amino acids in CCD/DBD (45.6% of full-length STAT1) to alanine and tested the mutants for STAT1 transcriptional activity.</p></sec><sec id="S4"><title>Results</title><p id="P5">Of these 342 mutants, 201 were neutral, 30 LOF, and 111 GOF in a luciferase assay. This assay system correctly estimated all previously reported LOF mutations (100%) and slightly fewer GOF mutations (78.1%) in CCD/DBD of STAT1. We found that GOF alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer. This assay also precisely predicted the impact of two hypomorphic and dominant-negative mutations, E157K and G250E, in CCD of STAT1 that we found in two unrelated MSMD patients.</p></sec><sec id="S5"><title>Conclusion</title><p id="P6">Systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and impact of heterozygous missense mutations in <italic>STAT1</italic> identified in patients with severe infectious diseases, including mycobacterial and fungal diseases.</p></sec></abstract><abstract abstract-type="short" id="Abs2"><title>Capsule summary</title><p id="P7">Reference database based on the alanine-scanning assay is a useful tool for evaluating unknown variations in STAT1. Gain-of-function alanine mutants occurred at the interface of the antiparallel STAT1 dimer, suggesting that they destabilize this dimer.</p></abstract><kwd-group><kwd>STAT1</kwd><kwd>alanine-scanning</kwd><kwd>chronic mucocutaneous candidiasis</kwd><kwd>mendelian susceptibility to mycobacterial disease</kwd><kwd>reference database</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/MaghrebDataLibMedV2/Data/Pmc/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000148 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd -nk 000148 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= MaghrebDataLibMedV2
|flux= Pmc
|étape= Curation
|type= RBID
|clé= PMC:5471135
|texte= Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Curation/RBID.i -Sk "pubmed:28011069" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Curation/biblio.hfd \
| NlmPubMed2Wicri -a MaghrebDataLibMedV2
| This area was generated with Dilib version V0.6.38. |  |