Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study
Identifieur interne : 001E21 ( Main/Exploration ); précédent : 001E20; suivant : 001E22Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study
Auteurs : Donato Iacovazzo ; Richard Caswell ; Benjamin Bunce ; Sian Jose ; Bo Yuan [États-Unis] ; Laura C. Hernández-Ramírez [États-Unis] ; Sonal Kapur ; Francisca Caimari ; Jane Evanson ; Francesco Ferraù ; Mary N. Dang ; Plamena Gabrovska ; Sarah J. Larkin [Royaume-Uni] ; Olaf Ansorge [Royaume-Uni] ; Celia Rodd [Canada] ; Mary L. Vance [États-Unis] ; Claudia Ramírez-Renteria [Mexique] ; Moisés Mercado [Mexique] ; Anthony P. Goldstone [Royaume-Uni] ; Michael Buchfelder [Allemagne] ; Christine P. Burren ; Alper Gurlek [Turquie] ; Pinaki Dutta [Inde] ; Catherine S. Choong [Australie] ; Timothy Cheetham ; Giampaolo Trivellin [États-Unis] ; Constantine A. Stratakis [États-Unis] ; Maria-Beatriz Lopes [États-Unis] ; Ashley B. Grossman [Royaume-Uni] ; Jacqueline Trouillas [France] ; James R. Lupski [États-Unis] ; Sian Ellard ; Julian R. Sampson ; Federico Roncaroli [Royaume-Uni] ; Márta KorbonitsSource :
- Acta Neuropathologica Communications [ 2051-5960 ] ; 2016.
Descripteurs français
- KwdFr :
- Acromégalie (), Acromégalie (anatomopathologie), Acromégalie (génétique), Adolescent, Adénomes (), Adénomes (anatomopathologie), Adénomes (génétique), Duplication de gène, Enfant, Enfant d'âge préscolaire, Femelle, Gigantisme (), Gigantisme (anatomopathologie), Gigantisme (génétique), Humains, Jeune adulte, Mutation germinale, Mâle, Nourrisson, Protéines et peptides de signalisation intracellulaire (génétique), Récepteurs couplés aux protéines G (génétique), Résultat thérapeutique, Tumeurs de l'hypophyse (), Tumeurs de l'hypophyse (anatomopathologie), Tumeurs de l'hypophyse (génétique).
- MESH :
- anatomopathologie : Acromégalie, Adénomes, Gigantisme, Tumeurs de l'hypophyse.
- génétique : Acromégalie, Adénomes, Gigantisme, Protéines et peptides de signalisation intracellulaire, Récepteurs couplés aux protéines G, Tumeurs de l'hypophyse.
- Acromégalie, Adolescent, Adénomes, Duplication de gène, Enfant, Enfant d'âge préscolaire, Femelle, Gigantisme, Humains, Jeune adulte, Mutation germinale, Mâle, Nourrisson, Résultat thérapeutique, Tumeurs de l'hypophyse.
English descriptors
- KwdEn :
- Acromegaly (complications), Acromegaly (genetics), Acromegaly (pathology), Adenoma (complications), Adenoma (genetics), Adenoma (pathology), Adolescent, Child, Child, Preschool, Female, Gene Duplication, Germ-Line Mutation, Gigantism (complications), Gigantism (genetics), Gigantism (pathology), Gigantism (therapy), Humans, Infant, Intracellular Signaling Peptides and Proteins (genetics), Male, Pituitary Neoplasms (complications), Pituitary Neoplasms (genetics), Pituitary Neoplasms (pathology), Receptors, G-Protein-Coupled (genetics), Treatment Outcome, Young Adult.
- MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Receptors, G-Protein-Coupled.
- complications : Acromegaly, Adenoma, Gigantism, Pituitary Neoplasms.
- genetics : Acromegaly, Adenoma, Gigantism, Pituitary Neoplasms.
- pathology : Acromegaly, Adenoma, Gigantism, Pituitary Neoplasms.
- therapy : Gigantism.
- Adolescent, Child, Child, Preschool, Female, Gene Duplication, Germ-Line Mutation, Humans, Infant, Male, Treatment Outcome, Young Adult.
Abstract
Non-syndromic pituitary gigantism can result from
We studied 153 patients (58 females and 95 males) with pituitary gigantism.
We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained
In conclusion, XLAG can result from germline or somatic duplication of
The online version of this article (doi:10.1186/s40478-016-0328-1) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s40478-016-0328-1
PubMed: 27245663
PubMed Central: 4888203
Affiliations:
- Allemagne, Australie, Canada, France, Inde, Mexique, Royaume-Uni, Turquie, États-Unis
- Angleterre, Grand Manchester, Manitoba, Maryland, Oxfordshire, Texas
- Manchester, Oxford, Winnipeg
- Université d'Oxford, Université de Manchester, Université du Manitoba
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Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Germline or somatic <italic>GPR101</italic>
duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study</title>
<author><name sortKey="Iacovazzo, Donato" sort="Iacovazzo, Donato" uniqKey="Iacovazzo D" first="Donato" last="Iacovazzo">Donato Iacovazzo</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
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<author><name sortKey="Caswell, Richard" sort="Caswell, Richard" uniqKey="Caswell R" first="Richard" last="Caswell">Richard Caswell</name>
<affiliation><nlm:aff id="Aff2">Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW UK</nlm:aff>
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<author><name sortKey="Bunce, Benjamin" sort="Bunce, Benjamin" uniqKey="Bunce B" first="Benjamin" last="Bunce">Benjamin Bunce</name>
<affiliation><nlm:aff id="Aff2">Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW UK</nlm:aff>
<wicri:noCountry code="subfield">EX2 5DW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Jose, Sian" sort="Jose, Sian" uniqKey="Jose S" first="Sian" last="Jose">Sian Jose</name>
<affiliation><nlm:aff id="Aff3">Institute of Medical Genetics, Cardiff University, Cardiff, CF14 4XN UK</nlm:aff>
<wicri:noCountry code="subfield">CF14 4XN UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Yuan, Bo" sort="Yuan, Bo" uniqKey="Yuan B" first="Bo" last="Yuan">Bo Yuan</name>
<affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hernandez Ramirez, Laura C" sort="Hernandez Ramirez, Laura C" uniqKey="Hernandez Ramirez L" first="Laura C." last="Hernández-Ramírez">Laura C. Hernández-Ramírez</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff5">Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kapur, Sonal" sort="Kapur, Sonal" uniqKey="Kapur S" first="Sonal" last="Kapur">Sonal Kapur</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Caimari, Francisca" sort="Caimari, Francisca" uniqKey="Caimari F" first="Francisca" last="Caimari">Francisca Caimari</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Evanson, Jane" sort="Evanson, Jane" uniqKey="Evanson J" first="Jane" last="Evanson">Jane Evanson</name>
<affiliation><nlm:aff id="Aff6">Department of Radiology, Barts Health NHS Trust, London, EC1A 7BE UK</nlm:aff>
<wicri:noCountry code="subfield">EC1A 7BE UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Ferrau, Francesco" sort="Ferrau, Francesco" uniqKey="Ferrau F" first="Francesco" last="Ferraù">Francesco Ferraù</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Dang, Mary N" sort="Dang, Mary N" uniqKey="Dang M" first="Mary N." last="Dang">Mary N. Dang</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gabrovska, Plamena" sort="Gabrovska, Plamena" uniqKey="Gabrovska P" first="Plamena" last="Gabrovska">Plamena Gabrovska</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Larkin, Sarah J" sort="Larkin, Sarah J" uniqKey="Larkin S" first="Sarah J." last="Larkin">Sarah J. Larkin</name>
<affiliation wicri:level="4"><nlm:aff id="Aff7">Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX1 2JD UK</nlm:aff>
<orgName type="university">Université d'Oxford</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ansorge, Olaf" sort="Ansorge, Olaf" uniqKey="Ansorge O" first="Olaf" last="Ansorge">Olaf Ansorge</name>
<affiliation wicri:level="4"><nlm:aff id="Aff7">Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX1 2JD UK</nlm:aff>
<orgName type="university">Université d'Oxford</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rodd, Celia" sort="Rodd, Celia" uniqKey="Rodd C" first="Celia" last="Rodd">Celia Rodd</name>
<affiliation wicri:level="4"><nlm:aff id="Aff8">Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3T 2 N2 Canada</nlm:aff>
<orgName type="university">Université du Manitoba</orgName>
<country>Canada</country>
<placeName><settlement type="city">Winnipeg</settlement>
<region type="state">Manitoba</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vance, Mary L" sort="Vance, Mary L" uniqKey="Vance M" first="Mary L." last="Vance">Mary L. Vance</name>
<affiliation wicri:level="1"><nlm:aff id="Aff9">Department of Endocrinology, University of Virginia, Charlottesville, 22908 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Endocrinology, University of Virginia, Charlottesville</wicri:regionArea>
<wicri:noRegion>Charlottesville</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ramirez Renteria, Claudia" sort="Ramirez Renteria, Claudia" uniqKey="Ramirez Renteria C" first="Claudia" last="Ramírez-Renteria">Claudia Ramírez-Renteria</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City, 06720 Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mercado, Moises" sort="Mercado, Moises" uniqKey="Mercado M" first="Moisés" last="Mercado">Moisés Mercado</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City, 06720 Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Goldstone, Anthony P" sort="Goldstone, Anthony P" uniqKey="Goldstone A" first="Anthony P." last="Goldstone">Anthony P. Goldstone</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, W12 0HS London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, W12 0HS London</wicri:regionArea>
<wicri:noRegion>W12 0HS London</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buchfelder, Michael" sort="Buchfelder, Michael" uniqKey="Buchfelder M" first="Michael" last="Buchfelder">Michael Buchfelder</name>
<affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Neurosurgery, University of Duisburg-Essen, Essen, 45141 Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurosurgery, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Burren, Christine P" sort="Burren, Christine P" uniqKey="Burren C" first="Christine P." last="Burren">Christine P. Burren</name>
<affiliation><nlm:aff id="Aff13">Department of Paediatric Endocrinology, University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW UK</nlm:aff>
<wicri:noCountry code="subfield">BS2 8HW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gurlek, Alper" sort="Gurlek, Alper" uniqKey="Gurlek A" first="Alper" last="Gurlek">Alper Gurlek</name>
<affiliation wicri:level="1"><nlm:aff id="Aff14">Department of Endocrinology and Metabolism, Faculty of Medicine, Hacettepe University, Ankara, 06100 Turkey</nlm:aff>
<country xml:lang="fr">Turquie</country>
<wicri:regionArea>Department of Endocrinology and Metabolism, Faculty of Medicine, Hacettepe University, Ankara</wicri:regionArea>
<wicri:noRegion>Ankara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dutta, Pinaki" sort="Dutta, Pinaki" uniqKey="Dutta P" first="Pinaki" last="Dutta">Pinaki Dutta</name>
<affiliation wicri:level="1"><nlm:aff id="Aff15">Department of Endocrinology, PGIMER, Chandigarh, 160012 India</nlm:aff>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Endocrinology, PGIMER, Chandigarh</wicri:regionArea>
<wicri:noRegion>Chandigarh</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Choong, Catherine S" sort="Choong, Catherine S" uniqKey="Choong C" first="Catherine S." last="Choong">Catherine S. Choong</name>
<affiliation wicri:level="1"><nlm:aff id="Aff16">Department of Pediatric Endocrinology, Princess Margaret Hospital for Children, Subiaco, 6008 Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Pediatric Endocrinology, Princess Margaret Hospital for Children, Subiaco</wicri:regionArea>
<wicri:noRegion>Subiaco</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cheetham, Timothy" sort="Cheetham, Timothy" uniqKey="Cheetham T" first="Timothy" last="Cheetham">Timothy Cheetham</name>
<affiliation><nlm:aff id="Aff17">Newcastle University c/o Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, NE1 4LP UK</nlm:aff>
<wicri:noCountry code="subfield">NE1 4LP UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Trivellin, Giampaolo" sort="Trivellin, Giampaolo" uniqKey="Trivellin G" first="Giampaolo" last="Trivellin">Giampaolo Trivellin</name>
<affiliation><nlm:aff id="Aff5">Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892 USA</nlm:aff>
<wicri:noCountry code="subfield">MD 20892 USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Stratakis, Constantine A" sort="Stratakis, Constantine A" uniqKey="Stratakis C" first="Constantine A." last="Stratakis">Constantine A. Stratakis</name>
<affiliation><nlm:aff id="Aff5">Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892 USA</nlm:aff>
<wicri:noCountry code="subfield">MD 20892 USA</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Lopes, Maria Beatriz" sort="Lopes, Maria Beatriz" uniqKey="Lopes M" first="Maria-Beatriz" last="Lopes">Maria-Beatriz Lopes</name>
<affiliation wicri:level="1"><nlm:aff id="Aff18">Department of Pathology, University of Virginia, Charlottesville, 22908 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Virginia, Charlottesville</wicri:regionArea>
<wicri:noRegion>Charlottesville</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Grossman, Ashley B" sort="Grossman, Ashley B" uniqKey="Grossman A" first="Ashley B." last="Grossman">Ashley B. Grossman</name>
<affiliation wicri:level="4"><nlm:aff id="Aff19">Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX1 2JD UK</nlm:aff>
<orgName type="university">Université d'Oxford</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Trouillas, Jacqueline" sort="Trouillas, Jacqueline" uniqKey="Trouillas J" first="Jacqueline" last="Trouillas">Jacqueline Trouillas</name>
<affiliation wicri:level="1"><nlm:aff id="Aff20">Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, 69500 France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron</wicri:regionArea>
<wicri:noRegion>Bron</wicri:noRegion>
<wicri:noRegion>Bron</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R." last="Lupski">James R. Lupski</name>
<affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff21">Department of Pediatrics, Baylor College of Medicine Houston, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Baylor College of Medicine Houston, Houston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff22">Human Genome Sequencing Center, Baylor College of Medicine Houston, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Human Genome Sequencing Center, Baylor College of Medicine Houston, Houston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff23">Texas Children’s Hospital, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Texas Children’s Hospital, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ellard, Sian" sort="Ellard, Sian" uniqKey="Ellard S" first="Sian" last="Ellard">Sian Ellard</name>
<affiliation><nlm:aff id="Aff2">Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW UK</nlm:aff>
<wicri:noCountry code="subfield">EX2 5DW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Sampson, Julian R" sort="Sampson, Julian R" uniqKey="Sampson J" first="Julian R." last="Sampson">Julian R. Sampson</name>
<affiliation><nlm:aff id="Aff3">Institute of Medical Genetics, Cardiff University, Cardiff, CF14 4XN UK</nlm:aff>
<wicri:noCountry code="subfield">CF14 4XN UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Roncaroli, Federico" sort="Roncaroli, Federico" uniqKey="Roncaroli F" first="Federico" last="Roncaroli">Federico Roncaroli</name>
<affiliation wicri:level="4"><nlm:aff id="Aff24">Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, M13 9PL UK</nlm:aff>
<orgName type="university">Université de Manchester</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Manchester</settlement>
<region type="nation">Angleterre</region>
<region nuts="2" type="region">Grand Manchester</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Korbonits, Marta" sort="Korbonits, Marta" uniqKey="Korbonits M" first="Márta" last="Korbonits">Márta Korbonits</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">27245663</idno>
<idno type="pmc">4888203</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888203</idno>
<idno type="RBID">PMC:4888203</idno>
<idno type="doi">10.1186/s40478-016-0328-1</idno>
<date when="2016">2016</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Germline or somatic <italic>GPR101</italic>
duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study</title>
<author><name sortKey="Iacovazzo, Donato" sort="Iacovazzo, Donato" uniqKey="Iacovazzo D" first="Donato" last="Iacovazzo">Donato Iacovazzo</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Caswell, Richard" sort="Caswell, Richard" uniqKey="Caswell R" first="Richard" last="Caswell">Richard Caswell</name>
<affiliation><nlm:aff id="Aff2">Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW UK</nlm:aff>
<wicri:noCountry code="subfield">EX2 5DW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Bunce, Benjamin" sort="Bunce, Benjamin" uniqKey="Bunce B" first="Benjamin" last="Bunce">Benjamin Bunce</name>
<affiliation><nlm:aff id="Aff2">Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW UK</nlm:aff>
<wicri:noCountry code="subfield">EX2 5DW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Jose, Sian" sort="Jose, Sian" uniqKey="Jose S" first="Sian" last="Jose">Sian Jose</name>
<affiliation><nlm:aff id="Aff3">Institute of Medical Genetics, Cardiff University, Cardiff, CF14 4XN UK</nlm:aff>
<wicri:noCountry code="subfield">CF14 4XN UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Yuan, Bo" sort="Yuan, Bo" uniqKey="Yuan B" first="Bo" last="Yuan">Bo Yuan</name>
<affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hernandez Ramirez, Laura C" sort="Hernandez Ramirez, Laura C" uniqKey="Hernandez Ramirez L" first="Laura C." last="Hernández-Ramírez">Laura C. Hernández-Ramírez</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff5">Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Kapur, Sonal" sort="Kapur, Sonal" uniqKey="Kapur S" first="Sonal" last="Kapur">Sonal Kapur</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Caimari, Francisca" sort="Caimari, Francisca" uniqKey="Caimari F" first="Francisca" last="Caimari">Francisca Caimari</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Evanson, Jane" sort="Evanson, Jane" uniqKey="Evanson J" first="Jane" last="Evanson">Jane Evanson</name>
<affiliation><nlm:aff id="Aff6">Department of Radiology, Barts Health NHS Trust, London, EC1A 7BE UK</nlm:aff>
<wicri:noCountry code="subfield">EC1A 7BE UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Ferrau, Francesco" sort="Ferrau, Francesco" uniqKey="Ferrau F" first="Francesco" last="Ferraù">Francesco Ferraù</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Dang, Mary N" sort="Dang, Mary N" uniqKey="Dang M" first="Mary N." last="Dang">Mary N. Dang</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gabrovska, Plamena" sort="Gabrovska, Plamena" uniqKey="Gabrovska P" first="Plamena" last="Gabrovska">Plamena Gabrovska</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Larkin, Sarah J" sort="Larkin, Sarah J" uniqKey="Larkin S" first="Sarah J." last="Larkin">Sarah J. Larkin</name>
<affiliation wicri:level="4"><nlm:aff id="Aff7">Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX1 2JD UK</nlm:aff>
<orgName type="university">Université d'Oxford</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ansorge, Olaf" sort="Ansorge, Olaf" uniqKey="Ansorge O" first="Olaf" last="Ansorge">Olaf Ansorge</name>
<affiliation wicri:level="4"><nlm:aff id="Aff7">Department of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX1 2JD UK</nlm:aff>
<orgName type="university">Université d'Oxford</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rodd, Celia" sort="Rodd, Celia" uniqKey="Rodd C" first="Celia" last="Rodd">Celia Rodd</name>
<affiliation wicri:level="4"><nlm:aff id="Aff8">Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba R3T 2 N2 Canada</nlm:aff>
<orgName type="university">Université du Manitoba</orgName>
<country>Canada</country>
<placeName><settlement type="city">Winnipeg</settlement>
<region type="state">Manitoba</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vance, Mary L" sort="Vance, Mary L" uniqKey="Vance M" first="Mary L." last="Vance">Mary L. Vance</name>
<affiliation wicri:level="1"><nlm:aff id="Aff9">Department of Endocrinology, University of Virginia, Charlottesville, 22908 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Endocrinology, University of Virginia, Charlottesville</wicri:regionArea>
<wicri:noRegion>Charlottesville</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ramirez Renteria, Claudia" sort="Ramirez Renteria, Claudia" uniqKey="Ramirez Renteria C" first="Claudia" last="Ramírez-Renteria">Claudia Ramírez-Renteria</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City, 06720 Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mercado, Moises" sort="Mercado, Moises" uniqKey="Mercado M" first="Moisés" last="Mercado">Moisés Mercado</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City, 06720 Mexico</nlm:aff>
<country xml:lang="fr">Mexique</country>
<wicri:regionArea>Endocrinology Service and Experimental Endocrinology Unit, Hospital de Especialidades Centro Médico Nacional Siglo XXI, IMSS, UNAM, Mexico City</wicri:regionArea>
<wicri:noRegion>Mexico City</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Goldstone, Anthony P" sort="Goldstone, Anthony P" uniqKey="Goldstone A" first="Anthony P." last="Goldstone">Anthony P. Goldstone</name>
<affiliation wicri:level="1"><nlm:aff id="Aff11">Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, W12 0HS London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust, W12 0HS London</wicri:regionArea>
<wicri:noRegion>W12 0HS London</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Buchfelder, Michael" sort="Buchfelder, Michael" uniqKey="Buchfelder M" first="Michael" last="Buchfelder">Michael Buchfelder</name>
<affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Neurosurgery, University of Duisburg-Essen, Essen, 45141 Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Neurosurgery, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Burren, Christine P" sort="Burren, Christine P" uniqKey="Burren C" first="Christine P." last="Burren">Christine P. Burren</name>
<affiliation><nlm:aff id="Aff13">Department of Paediatric Endocrinology, University Hospitals Bristol NHS Foundation Trust, Bristol, BS2 8HW UK</nlm:aff>
<wicri:noCountry code="subfield">BS2 8HW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Gurlek, Alper" sort="Gurlek, Alper" uniqKey="Gurlek A" first="Alper" last="Gurlek">Alper Gurlek</name>
<affiliation wicri:level="1"><nlm:aff id="Aff14">Department of Endocrinology and Metabolism, Faculty of Medicine, Hacettepe University, Ankara, 06100 Turkey</nlm:aff>
<country xml:lang="fr">Turquie</country>
<wicri:regionArea>Department of Endocrinology and Metabolism, Faculty of Medicine, Hacettepe University, Ankara</wicri:regionArea>
<wicri:noRegion>Ankara</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dutta, Pinaki" sort="Dutta, Pinaki" uniqKey="Dutta P" first="Pinaki" last="Dutta">Pinaki Dutta</name>
<affiliation wicri:level="1"><nlm:aff id="Aff15">Department of Endocrinology, PGIMER, Chandigarh, 160012 India</nlm:aff>
<country xml:lang="fr">Inde</country>
<wicri:regionArea>Department of Endocrinology, PGIMER, Chandigarh</wicri:regionArea>
<wicri:noRegion>Chandigarh</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Choong, Catherine S" sort="Choong, Catherine S" uniqKey="Choong C" first="Catherine S." last="Choong">Catherine S. Choong</name>
<affiliation wicri:level="1"><nlm:aff id="Aff16">Department of Pediatric Endocrinology, Princess Margaret Hospital for Children, Subiaco, 6008 Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Pediatric Endocrinology, Princess Margaret Hospital for Children, Subiaco</wicri:regionArea>
<wicri:noRegion>Subiaco</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cheetham, Timothy" sort="Cheetham, Timothy" uniqKey="Cheetham T" first="Timothy" last="Cheetham">Timothy Cheetham</name>
<affiliation><nlm:aff id="Aff17">Newcastle University c/o Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, NE1 4LP UK</nlm:aff>
<wicri:noCountry code="subfield">NE1 4LP UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Trivellin, Giampaolo" sort="Trivellin, Giampaolo" uniqKey="Trivellin G" first="Giampaolo" last="Trivellin">Giampaolo Trivellin</name>
<affiliation wicri:level="2"><nlm:aff id="Aff5">Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Stratakis, Constantine A" sort="Stratakis, Constantine A" uniqKey="Stratakis C" first="Constantine A." last="Stratakis">Constantine A. Stratakis</name>
<affiliation wicri:level="2"><nlm:aff id="Aff5">Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD 20892 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, Bethesda</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Lopes, Maria Beatriz" sort="Lopes, Maria Beatriz" uniqKey="Lopes M" first="Maria-Beatriz" last="Lopes">Maria-Beatriz Lopes</name>
<affiliation wicri:level="1"><nlm:aff id="Aff18">Department of Pathology, University of Virginia, Charlottesville, 22908 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology, University of Virginia, Charlottesville</wicri:regionArea>
<wicri:noRegion>Charlottesville</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Grossman, Ashley B" sort="Grossman, Ashley B" uniqKey="Grossman A" first="Ashley B." last="Grossman">Ashley B. Grossman</name>
<affiliation wicri:level="4"><nlm:aff id="Aff19">Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX1 2JD UK</nlm:aff>
<orgName type="university">Université d'Oxford</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Oxford</settlement>
<region type="nation">Angleterre</region>
<region type="région" nuts="1">Oxfordshire</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Trouillas, Jacqueline" sort="Trouillas, Jacqueline" uniqKey="Trouillas J" first="Jacqueline" last="Trouillas">Jacqueline Trouillas</name>
<affiliation wicri:level="1"><nlm:aff id="Aff20">Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, 69500 France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron</wicri:regionArea>
<wicri:noRegion>Bron</wicri:noRegion>
<wicri:noRegion>Bron</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lupski, James R" sort="Lupski, James R" uniqKey="Lupski J" first="James R." last="Lupski">James R. Lupski</name>
<affiliation wicri:level="2"><nlm:aff id="Aff4">Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Molecular and Human Genetics, Baylor College of Medicine, Houston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff21">Department of Pediatrics, Baylor College of Medicine Houston, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Baylor College of Medicine Houston, Houston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff22">Human Genome Sequencing Center, Baylor College of Medicine Houston, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Human Genome Sequencing Center, Baylor College of Medicine Houston, Houston</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff23">Texas Children’s Hospital, Houston, TX 77030 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
<wicri:cityArea>Texas Children’s Hospital, Houston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ellard, Sian" sort="Ellard, Sian" uniqKey="Ellard S" first="Sian" last="Ellard">Sian Ellard</name>
<affiliation><nlm:aff id="Aff2">Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, EX2 5DW UK</nlm:aff>
<wicri:noCountry code="subfield">EX2 5DW UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Sampson, Julian R" sort="Sampson, Julian R" uniqKey="Sampson J" first="Julian R." last="Sampson">Julian R. Sampson</name>
<affiliation><nlm:aff id="Aff3">Institute of Medical Genetics, Cardiff University, Cardiff, CF14 4XN UK</nlm:aff>
<wicri:noCountry code="subfield">CF14 4XN UK</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Roncaroli, Federico" sort="Roncaroli, Federico" uniqKey="Roncaroli F" first="Federico" last="Roncaroli">Federico Roncaroli</name>
<affiliation wicri:level="4"><nlm:aff id="Aff24">Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, M13 9PL UK</nlm:aff>
<orgName type="university">Université de Manchester</orgName>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Manchester</settlement>
<region type="nation">Angleterre</region>
<region nuts="2" type="region">Grand Manchester</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Korbonits, Marta" sort="Korbonits, Marta" uniqKey="Korbonits M" first="Márta" last="Korbonits">Márta Korbonits</name>
<affiliation><nlm:aff id="Aff1">Centre for Endocrinology, Barts and The London School of Medicine, London, EC1M 6BQ UK</nlm:aff>
<wicri:noCountry code="subfield">EC1M 6BQ UK</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Acta Neuropathologica Communications</title>
<idno type="eISSN">2051-5960</idno>
<imprint><date when="2016">2016</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Acromegaly (complications)</term>
<term>Acromegaly (genetics)</term>
<term>Acromegaly (pathology)</term>
<term>Adenoma (complications)</term>
<term>Adenoma (genetics)</term>
<term>Adenoma (pathology)</term>
<term>Adolescent</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Female</term>
<term>Gene Duplication</term>
<term>Germ-Line Mutation</term>
<term>Gigantism (complications)</term>
<term>Gigantism (genetics)</term>
<term>Gigantism (pathology)</term>
<term>Gigantism (therapy)</term>
<term>Humans</term>
<term>Infant</term>
<term>Intracellular Signaling Peptides and Proteins (genetics)</term>
<term>Male</term>
<term>Pituitary Neoplasms (complications)</term>
<term>Pituitary Neoplasms (genetics)</term>
<term>Pituitary Neoplasms (pathology)</term>
<term>Receptors, G-Protein-Coupled (genetics)</term>
<term>Treatment Outcome</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Acromégalie ()</term>
<term>Acromégalie (anatomopathologie)</term>
<term>Acromégalie (génétique)</term>
<term>Adolescent</term>
<term>Adénomes ()</term>
<term>Adénomes (anatomopathologie)</term>
<term>Adénomes (génétique)</term>
<term>Duplication de gène</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Femelle</term>
<term>Gigantisme ()</term>
<term>Gigantisme (anatomopathologie)</term>
<term>Gigantisme (génétique)</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mutation germinale</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Protéines et peptides de signalisation intracellulaire (génétique)</term>
<term>Récepteurs couplés aux protéines G (génétique)</term>
<term>Résultat thérapeutique</term>
<term>Tumeurs de l'hypophyse ()</term>
<term>Tumeurs de l'hypophyse (anatomopathologie)</term>
<term>Tumeurs de l'hypophyse (génétique)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term>
<term>Receptors, G-Protein-Coupled</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Acromégalie</term>
<term>Adénomes</term>
<term>Gigantisme</term>
<term>Tumeurs de l'hypophyse</term>
</keywords>
<keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Acromegaly</term>
<term>Adenoma</term>
<term>Gigantism</term>
<term>Pituitary Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Acromegaly</term>
<term>Adenoma</term>
<term>Gigantism</term>
<term>Pituitary Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Acromégalie</term>
<term>Adénomes</term>
<term>Gigantisme</term>
<term>Protéines et peptides de signalisation intracellulaire</term>
<term>Récepteurs couplés aux protéines G</term>
<term>Tumeurs de l'hypophyse</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Acromegaly</term>
<term>Adenoma</term>
<term>Gigantism</term>
<term>Pituitary Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Gigantism</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Female</term>
<term>Gene Duplication</term>
<term>Germ-Line Mutation</term>
<term>Humans</term>
<term>Infant</term>
<term>Male</term>
<term>Treatment Outcome</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Acromégalie</term>
<term>Adolescent</term>
<term>Adénomes</term>
<term>Duplication de gène</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Femelle</term>
<term>Gigantisme</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Mutation germinale</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Résultat thérapeutique</term>
<term>Tumeurs de l'hypophyse</term>
</keywords>
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<front><div type="abstract" xml:lang="en"><p>Non-syndromic pituitary gigantism can result from <italic>AIP</italic>
mutations or the recently identified Xq26.3 microduplication causing X-linked acrogigantism (XLAG). Within Xq26.3, <italic>GPR101</italic>
is believed to be the causative gene, and the c.924G > C (p.E308D) variant in this orphan G protein-coupled receptor has been suggested to play a role in the pathogenesis of acromegaly.</p>
<p>We studied 153 patients (58 females and 95 males) with pituitary gigantism. <italic>AIP</italic>
mutation-negative cases were screened for <italic>GPR101</italic>
duplication through copy number variation droplet digital PCR and high-density aCGH. The genetic, clinical and histopathological features of XLAG patients were studied in detail. 395 peripheral blood and 193 pituitary tumor DNA samples from acromegaly patients were tested for <italic>GPR101</italic>
variants.</p>
<p>We identified 12 patients (10 females and 2 males; 7.8 %) with XLAG. In one subject, the duplicated region only contained <italic>GPR101</italic>
, but not the other three genes in found to be duplicated in the previously reported patients, defining a new smallest region of overlap of duplications. While females presented with germline mutations, the two male patients harbored the mutation in a mosaic state. Nine patients had pituitary adenomas, while three had hyperplasia. The comparison of the features of XLAG, <italic>AIP</italic>
-positive and <italic>GPR101</italic>
&<italic>AIP</italic>
-negative patients revealed significant differences in sex distribution, age at onset, height, prolactin co-secretion and histological features. The pathological features of XLAG-related adenomas were remarkably similar. These tumors had a sinusoidal and lobular architecture. Sparsely and densely granulated somatotrophs were admixed with lactotrophs; follicle-like structures and calcifications were commonly observed. Patients with sporadic of familial acromegaly did not have an increased prevalence of the c.924G > C (p.E308D) <italic>GPR101</italic>
variant compared to public databases.</p>
<p>In conclusion, XLAG can result from germline or somatic duplication of <italic>GPR101</italic>
. Duplication of <italic>GPR101</italic>
alone is sufficient for the development of XLAG, implicating it as the causative gene within the Xq26.3 region. The pathological features of XLAG-associated pituitary adenomas are typical and, together with the clinical phenotype, should prompt genetic testing.</p>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s40478-016-0328-1) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<name sortKey="Stratakis, Constantine A" sort="Stratakis, Constantine A" uniqKey="Stratakis C" first="Constantine A." last="Stratakis">Constantine A. Stratakis</name>
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<country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Larkin, Sarah J" sort="Larkin, Sarah J" uniqKey="Larkin S" first="Sarah J." last="Larkin">Sarah J. Larkin</name>
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<country name="Allemagne"><noRegion><name sortKey="Buchfelder, Michael" sort="Buchfelder, Michael" uniqKey="Buchfelder M" first="Michael" last="Buchfelder">Michael Buchfelder</name>
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<country name="Australie"><noRegion><name sortKey="Choong, Catherine S" sort="Choong, Catherine S" uniqKey="Choong C" first="Catherine S." last="Choong">Catherine S. Choong</name>
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<country name="France"><noRegion><name sortKey="Trouillas, Jacqueline" sort="Trouillas, Jacqueline" uniqKey="Trouillas J" first="Jacqueline" last="Trouillas">Jacqueline Trouillas</name>
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