Clinical Transcriptome Sequencing Confirms Activation of a Cryptic Splice Site in Suspected SYNGAP1-Related Disorder

Molecular syndromology

Elise Brimble¹ 

关键词: RNA sequencing;    SYNGAP1;    Transcriptome;    Variant interpretation;    Intronic variation;   

DOI  :  10.1159/000492706

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

SYNGAP1 encodes a brain-specific Ras GTPase activating protein (GAP) that regulates synaptic strength in glutamatergic neurons. Pathogenic variants in this gene are associated with a neurodevelopmental disorder characterized by intellectual and developmental disabilities, generalized epilepsy, hypotonia, and autism spectrum disorders. We describe a young male with suspected SYNGAP1-related disorder given clinical overlap and identification of an intronic variant of uncertain significance; clinical transcriptome analysis demonstrated activation of a cryptic acceptor splice site resulting in frameshift and introduction of a stop codon. This report highlights the utility of functional studies newly available to clinical practice in confirming a suspected genetic diagnosis, which can directly impact medical management and preclude the need for additional diagnostic testing.

【 授权许可】

CC BY