MaghrebDataLibMedV2, Main, Exploration, bibRecord, 000359

Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants

Identifieur interne : 000359 ( Main/Exploration ); précédent : 000358; suivant : 000360

Alanine-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.

RBID : PMC:5471135

Descripteurs français

KwdFr :
- Alanine (génétique), Domaines protéiques (MeSH), Dosage biologique (MeSH), Facteur de transcription STAT-1 (génétique), Femelle (MeSH), Humains (MeSH), Infections à Mycobacterium (génétique), Mutagenèse (MeSH), Mutation (MeSH), Mâle (MeSH), Prédisposition génétique à une maladie (MeSH).
MESH :
- génétique : Alanine, Facteur de transcription STAT-1, Infections à Mycobacterium.
- Domaines protéiques, Dosage biologique, Femelle, Humains, Mutagenèse, Mutation, Mâle, Prédisposition génétique à une maladie.

English descriptors

KwdEn :
- Alanine (genetics), Biological Assay (MeSH), Female (MeSH), Genetic Predisposition to Disease (MeSH), Humans (MeSH), Male (MeSH), Mutagenesis (MeSH), Mutation (MeSH), Mycobacterium Infections (genetics), Protein Domains (MeSH), STAT1 Transcription Factor (genetics).
MESH :
- chemical , genetics : Alanine, STAT1 Transcription Factor.
- genetics : Mycobacterium Infections.
- Biological Assay, Female, Genetic Predisposition to Disease, Humans, Male, Mutagenesis, Mutation, Protein Domains.

Abstract

Background

Germline heterozygous mutations in human STAT1 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 STAT1 mutation develop mycobacterial disease, obscuring the functional significance of the identified STAT1 mutations. Current computational approaches, such as combined annotation-dependent depletion, do not distinguish LOF and GOF variants

Objective

Estimate variations in CCD/DBD of STAT1

Method

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.

Results

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.

Conclusion

Systematic alanine-scanning assay is a useful tool to estimate the GOF or LOF status and impact of heterozygous missense mutations in STAT1 identified in patients with severe infectious diseases, including mycobacterial and fungal diseases.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471135

DOI: 10.1016/j.jaci.2016.09.035
PubMed: 28011069
PubMed Central: 5471135

Affiliations:

Argentine, France, Japon, Maroc, États-Unis

Le document en format XML

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<author><name sortKey="Kong, Xiao Fei" sort="Kong, Xiao Fei" uniqKey="Kong X" first="Xiao-Fei" last="Kong">Xiao-Fei Kong</name>
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<author><name sortKey="Ohnishi, Hidenori" sort="Ohnishi, Hidenori" uniqKey="Ohnishi H" first="Hidenori" last="Ohnishi">Hidenori Ohnishi</name>
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<author><name sortKey="El Baghdadi, Jamila" sort="El Baghdadi, Jamila" uniqKey="El Baghdadi J" first="Jamila" last="El Baghdadi">Jamila El Baghdadi</name>
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<author><name sortKey="Fujiwara, Kaori" sort="Fujiwara, Kaori" uniqKey="Fujiwara K" first="Kaori" last="Fujiwara">Kaori Fujiwara</name>
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<author><name sortKey="Oleastro, Matias" sort="Oleastro, Matias" uniqKey="Oleastro M" first="Matias" last="Oleastro">Matias Oleastro</name>
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<author><name sortKey="Perez, Laura" sort="Perez, Laura" uniqKey="Perez L" first="Laura" last="Perez">Laura Perez</name>
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<author><name sortKey="Takada, Hidetoshi" sort="Takada, Hidetoshi" uniqKey="Takada H" first="Hidetoshi" last="Takada">Hidetoshi Takada</name>
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<author><name sortKey="Hara, Toshiro" sort="Hara, Toshiro" uniqKey="Hara T" first="Toshiro" last="Hara">Toshiro Hara</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka</wicri:regionArea>
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<author><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
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<country xml:lang="fr">États-Unis</country>
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<affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff>
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<wicri:regionArea>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris</wicri:regionArea>
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<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>
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<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>
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<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>
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</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>
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<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>
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<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>
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<affiliation wicri:level="1"><nlm:aff id="A13">Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France</nlm:aff>
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<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>
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<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>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Alanine (genetics)</term>
<term>Biological Assay (MeSH)</term>
<term>Female (MeSH)</term>
<term>Genetic Predisposition to Disease (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Male (MeSH)</term>
<term>Mutagenesis (MeSH)</term>
<term>Mutation (MeSH)</term>
<term>Mycobacterium Infections (genetics)</term>
<term>Protein Domains (MeSH)</term>
<term>STAT1 Transcription Factor (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Alanine (génétique)</term>
<term>Domaines protéiques (MeSH)</term>
<term>Dosage biologique (MeSH)</term>
<term>Facteur de transcription STAT-1 (génétique)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Infections à Mycobacterium (génétique)</term>
<term>Mutagenèse (MeSH)</term>
<term>Mutation (MeSH)</term>
<term>Mâle (MeSH)</term>
<term>Prédisposition génétique à une maladie (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Alanine</term>
<term>STAT1 Transcription Factor</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Mycobacterium Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Alanine</term>
<term>Facteur de transcription STAT-1</term>
<term>Infections à Mycobacterium</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Biological Assay</term>
<term>Female</term>
<term>Genetic Predisposition to Disease</term>
<term>Humans</term>
<term>Male</term>
<term>Mutagenesis</term>
<term>Mutation</term>
<term>Protein Domains</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Domaines protéiques</term>
<term>Dosage biologique</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mutagenèse</term>
<term>Mutation</term>
<term>Mâle</term>
<term>Prédisposition génétique à une maladie</term>
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<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>
<affiliations><list><country><li>Argentine</li>
<li>France</li>
<li>Japon</li>
<li>Maroc</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="Japon"><noRegion><name sortKey="Kagawa, Reiko" sort="Kagawa, Reiko" uniqKey="Kagawa R" first="Reiko" last="Kagawa">Reiko Kagawa</name>
</noRegion>
<name sortKey="Fujiki, Ryoji" sort="Fujiki, Ryoji" uniqKey="Fujiki R" first="Ryoji" last="Fujiki">Ryoji Fujiki</name>
<name sortKey="Fujiwara, Kaori" sort="Fujiwara, Kaori" uniqKey="Fujiwara K" first="Kaori" last="Fujiwara">Kaori Fujiwara</name>
<name sortKey="Hara, Toshiro" sort="Hara, Toshiro" uniqKey="Hara T" first="Toshiro" last="Hara">Toshiro Hara</name>
<name sortKey="Hirata, Osamu" sort="Hirata, Osamu" uniqKey="Hirata O" first="Osamu" last="Hirata">Osamu Hirata</name>
<name sortKey="Ikeda, Maiko" sort="Ikeda, Maiko" uniqKey="Ikeda M" first="Maiko" last="Ikeda">Maiko Ikeda</name>
<name sortKey="Kato, Zenichiro" sort="Kato, Zenichiro" uniqKey="Kato Z" first="Zenichiro" last="Kato">Zenichiro Kato</name>
<name sortKey="Kato, Zenichiro" sort="Kato, Zenichiro" uniqKey="Kato Z" first="Zenichiro" last="Kato">Zenichiro Kato</name>
<name sortKey="Kobayashi, Masao" sort="Kobayashi, Masao" uniqKey="Kobayashi M" first="Masao" last="Kobayashi">Masao Kobayashi</name>
<name sortKey="Nishimura, Shiho" sort="Nishimura, Shiho" uniqKey="Nishimura S" first="Shiho" last="Nishimura">Shiho Nishimura</name>
<name sortKey="Ohara, Osamu" sort="Ohara, Osamu" uniqKey="Ohara O" first="Osamu" last="Ohara">Osamu Ohara</name>
<name sortKey="Ohara, Osamu" sort="Ohara, Osamu" uniqKey="Ohara O" first="Osamu" last="Ohara">Osamu Ohara</name>
<name sortKey="Ohnishi, Hidenori" sort="Ohnishi, Hidenori" uniqKey="Ohnishi H" first="Hidenori" last="Ohnishi">Hidenori Ohnishi</name>
<name sortKey="Okada, Satoshi" sort="Okada, Satoshi" uniqKey="Okada S" first="Satoshi" last="Okada">Satoshi Okada</name>
<name sortKey="Saito, Satoshi" sort="Saito, Satoshi" uniqKey="Saito S" first="Satoshi" last="Saito">Satoshi Saito</name>
<name sortKey="Sakata, Sonoko" sort="Sakata, Sonoko" uniqKey="Sakata S" first="Sonoko" last="Sakata">Sonoko Sakata</name>
<name sortKey="Takada, Hidetoshi" sort="Takada, Hidetoshi" uniqKey="Takada H" first="Hidetoshi" last="Takada">Hidetoshi Takada</name>
<name sortKey="Tsumura, Miyuki" sort="Tsumura, Miyuki" uniqKey="Tsumura M" first="Miyuki" last="Tsumura">Miyuki Tsumura</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Itan, Yuval" sort="Itan, Yuval" uniqKey="Itan Y" first="Yuval" last="Itan">Yuval Itan</name>
</noRegion>
<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Kong, Xiao Fei" sort="Kong, Xiao Fei" uniqKey="Kong X" first="Xiao-Fei" last="Kong">Xiao-Fei Kong</name>
<name sortKey="Okada, Satoshi" sort="Okada, Satoshi" uniqKey="Okada S" first="Satoshi" last="Okada">Satoshi Okada</name>
<name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
</country>
<country name="Maroc"><noRegion><name sortKey="El Baghdadi, Jamila" sort="El Baghdadi, Jamila" uniqKey="El Baghdadi J" first="Jamila" last="El Baghdadi">Jamila El Baghdadi</name>
</noRegion>
<name sortKey="Ailal, Fatima" sort="Ailal, Fatima" uniqKey="Ailal F" first="Fatima" last="Ailal">Fatima Ailal</name>
<name sortKey="Bousfiha, Aziz" sort="Bousfiha, Aziz" uniqKey="Bousfiha A" first="Aziz" last="Bousfiha">Aziz Bousfiha</name>
</country>
<country name="Argentine"><noRegion><name sortKey="Oleastro, Matias" sort="Oleastro, Matias" uniqKey="Oleastro M" first="Matias" last="Oleastro">Matias Oleastro</name>
</noRegion>
<name sortKey="Danielian, Silvia" sort="Danielian, Silvia" uniqKey="Danielian S" first="Silvia" last="Danielian">Silvia Danielian</name>
<name sortKey="Perez, Laura" sort="Perez, Laura" uniqKey="Perez L" first="Laura" last="Perez">Laura Perez</name>
<name sortKey="Yancoski, Judith" sort="Yancoski, Judith" uniqKey="Yancoski J" first="Judith" last="Yancoski">Judith Yancoski</name>
</country>
<country name="France"><noRegion><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
</noRegion>
<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
<name sortKey="Boisson Dupuis, Stephanie" sort="Boisson Dupuis, Stephanie" uniqKey="Boisson Dupuis S" first="Stéphanie" last="Boisson-Dupuis">Stéphanie Boisson-Dupuis</name>
<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<name sortKey="Bustamante, Jacinta" sort="Bustamante, Jacinta" uniqKey="Bustamante J" first="Jacinta" last="Bustamante">Jacinta Bustamante</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name>
<name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name>
</country>
</tree>
</affiliations>
</record>

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Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants

Alanine-scanning mutagenesis of human STAT1 to estimate loss- or gain-of-function variants

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