Richardson, R., Baralle, D., Bennett, C. et al. (19 more authors) (2022) Further delineation of phenotypic spectrum of SCN2A-related disorder. American Journal of Medical Genetics Part A, 188 (3). pp. 867-877. ISSN 1552-4825
Abstract
SCN2A-related disorders include intellectual disability, autism spectrum disorder, seizures, episodic ataxia, and schizophrenia. In this study, the phenotype–genotype association in SCN2A-related disorders was further delineated by collecting detailed clinical and molecular characteristics. Using previously proposed genotype–phenotype hypotheses based on variant function and position, the potential of phenotype prediction from the variants found was examined. Patients were identified through the Deciphering Developmental Disorders study and gene matching strategies. Phenotypic information and variant interpretation evidence were collated. Seventeen previously unreported patients and five patients who had been previously reported (but with minimal phenotypic and segregation data) were included (10 males, 12 females; median age 10.5 years). All patients had developmental delays and the majority had intellectual disabilities. Seizures were reported in 15 of 22 (68.2%), four of 22 (18.2%) had autism spectrum disorder and no patients were reported with episodic ataxia. The majority of variants were de novo. One family had presumed gonadal mosaicism. The correlation of the use of sodium channel-blocking antiepileptic drugs with phenotype or genotype was variable. These data suggest that variant type and position alone can provide some predictive information about the phenotype in a proportion of cases, but more precise assessment of variant function is needed for meaningful phenotype prediction.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Wiley Periodicals LLC. This is an author-produced version of a paper subsequently published in American Journal of Medical Genetics Part A. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | autism spectrum disorder; developmental delay; episodic ataxia; intellectual disability; SCN2A |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 26 Apr 2022 12:07 |
Last Modified: | 11 Dec 2022 01:13 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ajmg.a.62595 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:185792 |