Reem Al-Jawahiri1, Aidin Foroutan2, Jennifer Kerkhof2, Haley McConkey2, Michael Levy2, Sadegheh Haghshenas2, Kathleen Rooney2, Jasmin Turner3, Debbie Shears4, Muriel Holder5, Henrietta Lefroy6, Bruce Castle6, Linda M Reis7, Elena V Semina7, Katherine Lachlan8, Kate Chandler9, Thomas Wright9, Jill Clayton-Smith9, Franziska Phan Hug10, Nelly Pitteloud10, Lucia Bartoloni10, Sabine Hoffjan11, Soo-Mi Park12, Ajay Thankamony12, Melissa Lees13, Emma Wakeling13, Swati Naik14, Britta Hanker15, Katta M Girisha16, Emanuele Agolini17, Zampino Giuseppe18, Ziegler Alban19, Marine Tessarech19, Boris Keren20, Alexandra Afenjar20, Christiane Zweier21, Andre Reis21, Thomas Smol22, Yoshinori Tsurusaki23, Okamoto Nobuhiko24, Futoshi Sekiguchi25, Naomi Tsuchida25, Naomichi Matsumoto25, Ikuyo Kou26, Yoshiro Yonezawa27, Shiro Ikegawa26, Bert Callewaert28, Megan Freeth1, Lotte Kleinendorst29, Alan Donaldson30, Marielle Alders31, Anne De Paepe32, Bekim Sadikovic33, Alisdair McNeill34. 1. Department of Psychology, The University of Sheffield, Sheffield, United Kingdom. 2. 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. 3. Biosciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom. 4. Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 5. Department of Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. 6. Peninsula Clinical Genetics Service, RD&E Heavitree Hospital, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom. 7. Department of Pediatrics and Children's Research Institute, Medical College of Wisconsin, Children's Wisconsin, Milwaukee, WI. 8. Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. 9. Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 10. Service of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland. 11. Ruhr-Universitat Bochum, Abteilung für Humangenetik, Bochum, Germany. 12. Clinical Genetics, Addenbrooke's Treatment Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 13. Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 14. West Midlands Regional Clinical Genetics Centre and Department of Clinical Genetics, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, United Kingdom. 15. Ambulanzzentrum UKSH, Institut für Humangenetik, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany. 16. Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India. 17. Medical Genetics Laboratory, Bambino Gesu Children's Hospital, Rome, Italy. 18. Paediatric Department, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 19. Angers University Hospital Center, Angers, France. 20. Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 21. Department of Human Genetics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 22. EA7364 RADEME, Institute of Medical Genetics, Lille University Hospital, Lille University, Lille, France. 23. Faculty of Nutritional Science, Sagami Women's University, Sagamihara, Japan. 24. Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan. 25. Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. 26. Laboratory for Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan. 27. 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. 28. Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium; Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. 29. Centrum voor Medische Genetica - UZ Gent, Ghent University Hospital, Gent, Belgium. 30. Department of Clinical Genetics Service, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom. 31. Department of Human Genetics, Amsterdam Reproduction & Development Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. 32. Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium. 33. Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada. Electronic address: Bekim.Sadikovic@lhsc.on.ca. 34. 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.
Abstract
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.
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.
Authors: S Anazi; S Maddirevula; E Faqeih; H Alsedairy; F Alzahrani; H E Shamseldin; N Patel; M Hashem; N Ibrahim; F Abdulwahab; N Ewida; H S Alsaif; H Al Sharif; W Alamoudi; A Kentab; F A Bashiri; M Alnaser; A H AlWadei; M Alfadhel; W Eyaid; A Hashem; A Al Asmari; M M Saleh; A AlSaman; K A Alhasan; M Alsughayir; M Al Shammari; A Mahmoud; Z N Al-Hassnan; M Al-Husain; R Osama Khalil; N Abd El Meguid; A Masri; R Ali; T Ben-Omran; P El Fishway; A Hashish; A Ercan Sencicek; M State; A M Alazami; M A Salih; N Altassan; S T Arold; M Abouelhoda; S M Wakil; D Monies; R Shaheen; F S Alkuraya Journal: Mol Psychiatry Date: 2016-07-19 Impact factor: 15.992
Authors: Yasmine Neirijnck; Antoine Reginensi; Kirsten Y Renkema; Filippo Massa; Vladimir M Kozlov; Haroun Dhib; Ernie M H F Bongers; Wout F Feitz; Albertien M van Eerde; Veronique Lefebvre; Nine V A M Knoers; Mansoureh Tabatabaei; Herbert Schulz; Helen McNeill; Franz Schaefer; Michael Wegner; Elisabeth Sock; Andreas Schedl Journal: Kidney Int Date: 2018-02-17 Impact factor: 10.612
Authors: Caroline F Wright; Tomas W Fitzgerald; Wendy D Jones; Stephen Clayton; Jeremy F McRae; Margriet van Kogelenberg; Daniel A King; Kirsty Ambridge; Daniel M Barrett; Tanya Bayzetinova; A Paul Bevan; Eugene Bragin; Eleni A Chatzimichali; Susan Gribble; Philip Jones; Netravathi Krishnappa; Laura E Mason; Ray Miller; Katherine I Morley; Vijaya Parthiban; Elena Prigmore; Diana Rajan; Alejandro Sifrim; G Jawahar Swaminathan; Adrian R Tivey; Anna Middleton; Michael Parker; Nigel P Carter; Jeffrey C Barrett; Matthew E Hurles; David R FitzPatrick; Helen V Firth Journal: Lancet Date: 2014-12-17 Impact factor: 79.321