SOX11 variants cause a neurodevelopmental disorder with infrequent ocular malformations and hypogonadotropic hypogonadism and with distinct DNA methylation profile.

Autor:	Al-Jawahiri R; Department of Psychology, The University of Sheffield, Sheffield, United Kingdom., Foroutan A; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; The Archie and Irene Verspeeten Clinical Genome Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada., Kerkhof J; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; The Archie and Irene Verspeeten Clinical Genome Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada., McConkey H; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; The Archie and Irene Verspeeten Clinical Genome Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada., Levy M; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; The Archie and Irene Verspeeten Clinical Genome Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada., Haghshenas S; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; The Archie and Irene Verspeeten Clinical Genome Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada., Rooney K; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada; The Archie and Irene Verspeeten Clinical Genome Centre, London Health Sciences Foundation, London Health Sciences Centre, London, Ontario, Canada., Turner J; Biosciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom., Shears D; Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom., Holder M; Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Lefroy H; Peninsula Clinical Genetics Service, RD&E Heavitree Hospital, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom., Castle B; Peninsula Clinical Genetics Service, RD&E Heavitree Hospital, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom., Reis LM; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI., Semina EV; Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI., Lachlan K; Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom., Chandler K; Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom., Wright T; Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom., Clayton-Smith J; Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom., Hug FP; Service of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland., Pitteloud N; Service of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland., Bartoloni L; Service of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland., Hoffjan S; Ruhr-Universitat Bochum, Abteilung für Humangenetik, Bochum, Germany., Park SM; Clinical Genetics, Addenbrooke's Treatment Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Thankamony A; Clinical Genetics, Addenbrooke's Treatment Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom., Lees M; Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom., Wakeling E; Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom., Naik S; West Midlands Regional Clinical Genetics Centre and Department of Clinical Genetics, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom., Hanker B; Ambulanzzentrum UKSH, Institut für Humangenetik, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany., Girisha KM; Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India., Agolini E; Medical Genetics Laboratory, Bambino Gesu Children's Hospital, Rome, Italy., Giuseppe Z; Paediatric Department, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy., Alban Z; Angers University Hospital Center, Angers, France., Tessarech M; Angers University Hospital Center, Angers, France., Keren B; Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Afenjar A; Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Zweier C; Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Reis A; Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Smol T; EA7364 RADEME, Institute of Medical Genetics, Lille University Hospital, Lille University, Lille, France., Tsurusaki Y; Faculty of Nutritional Science, Sagami Women's University, Sagamihara, Japan., Nobuhiko O; Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan., Sekiguchi F; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan., Tsuchida N; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan., Matsumoto N; Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan., Kou I; Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan., Yonezawa Y; Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan; Department of Orthopedic Surgery, Keio University School of Medicine, Keio University, Tokyo, Japan., Ikegawa S; Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan., Callewaert B; Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium., Freeth M; Department of Psychology, The University of Sheffield, Sheffield, United Kingdom., Kleinendorst L; Centrum voor Medische Genetica - UZ Gent, Ghent University Hospital, Gent, Belgium., Donaldson A; Department of Clinical Genetics Service, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom., Alders M; Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands., De Paepe A; Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium., Sadikovic B; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada. Electronic address: Bekim.Sadikovic@lhsc.on.ca., McNeill A; Department of Neuroscience, The Medical School, The University of Sheffield, Sheffield, United Kingdom; Department of Clinical Genetics, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom. Electronic address: a.mcneill@sheffield.ac.uk.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2022 Jun; Vol. 24 (6), pp. 1261-1273. Date of Electronic Publication: 2022 Mar 24.
DOI:	10.1016/j.gim.2022.02.013
Abstrakt:	Purpose: This study aimed to undertake a multidisciplinary characterization of the phenotype associated with SOX11 variants. Methods: Individuals with protein altering variants in SOX11 were identified through exome and genome sequencing and international data sharing. Deep clinical phenotyping was undertaken by referring clinicians. Blood DNA methylation was assessed using Infinium MethylationEPIC array. The expression pattern of SOX11 in developing human brain was defined using RNAscope. Results: We reported 38 new patients with SOX11 variants. Idiopathic hypogonadotropic hypogonadism was confirmed as a feature of SOX11 syndrome. A distinctive pattern of blood DNA methylation was identified in SOX11 syndrome, separating SOX11 syndrome from other BAFopathies. Conclusion: SOX11 syndrome is a distinct clinical entity with characteristic clinical features and episignature differentiating it from BAFopathies. Competing Interests: Conflict of Interest The authors declare no conflicts of interest. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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