SYT1-associated neurodevelopmental disorder: a case series

Author:

Baker Kate12,Gordon Sarah L3,Melland Holly3,Bumbak Fabian3,Scott Daniel J34,Jiang Tess J3,Owen David5,Turner Bradley J3,Boyd Stewart G6,Rossi Mari7,Al-Raqad Mohammed8,Elpeleg Orly9,Peck Dawn10,Mancini Grazia M S11,Wilke Martina11,Zollino Marcella12,Marangi Giuseppe12,Weigand Heike13,Borggraefe Ingo13,Haack Tobias1415,Stark Zornitza16,Sadedin Simon1617,Tan Tiong Yang16,Jiang Yunyun18,Gibbs Richard A18,Ellingwood Sara19,Amaral Michelle20,Kelley Whitley20,Kurian Manju A6,Cousin Michael A21,Raymond F Lucy1,

Affiliation:

1. Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Wellcome Trust / MRC Building, Hills Road, Cambridge, UK

2. MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge, UK

3. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade, Parkville, VIC, Australia

4. Department of Biochemistry and Molecular Biology, University of Melbourne, 30 Royal Parade, Parkville, VIC, Australia

5. Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Hills Road, Cambridge, UK

6. Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, UK

7. Ambry Genetics, 15 Argonaut, Aliso Viejo, CA, USA

8. Department of Clinical Genetics, Queen Rania Al-Abdullah Children Hospital, King Hussein Medical Centre, Royal Medical Services, Amman, Jordan

9. Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel

10. University of Missouri Health Care, Columbia, MO, USA

11. Department of Clinical Genetics, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands

12. Institute of Genomic Medicine, Catholic University, A. Gemelli Foundation, Roma, Italy

13. Department of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Dr. von Hauner’s Children’s Hospital, University of Munich, Munich, Germany

14. Institute of Human Genetics, Technische Universität München, Munich, Germany

15. Institute of Medical Genetics and Applied Genomics, University of Tuebingen, Tuebingen, Germany

16. Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Flemington Road, Parkville VIC, Australia

17. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA

18. Human Genome Sequencing Center, Baylor College of Medicine, Texas, USA

19. Maine Medical Partners Pediatric Specialty Care, Congress St, Portland ME, USA

20. HudsonAlpha Institute for Biotechnology, 601 Genome Way NW, Huntsville, AL, USA

21. Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh, UK

Abstract

Baker, Gordon et al. present the first international case series describing the neurodevelopmental disorder associated with Synaptotagmin 1 (SYT1) de novo missense mutations. Key features include movement abnormalities, severe intellectual disability, and hallmark EEG alterations. Expression of patients’ SYT1 mutations in mouse neurons disturbs presynaptic vesicle dynamics in a mutation-specific manner.

Funder

National Institute of Health Research

Medical Research Council

National Health and Medical Research Council of Australia

Victorian Government

Stafford Fox Medical Research Foundation

Wellcome Trust

National Human Genome Research Institute

National Eye Institute

National Heart, Lung and Blood Institute

Daniel MacArthur and Heidi Rehm

Undiagnosed Diseases Program-Victoria

US National Human Genome Research Institute

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

Reference37 articles.

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3. De novo gain-of-function and loss-of-function mutations of SCN8A in patients with intellectual disabilities and epilepsy;Blanchard;J Med Genet,2015

4. Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome;Cafiero;Eur J Hum Genet,2015

5. The evolving spectrum of PRRT2-associated paroxysmal diseases;Ebrahimi-Fakhari;Brain,2015

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