Open AccessClinical Transcriptome Sequencing Confirms Activation of a Cryptic Splice Site in Suspected SYNGAP1-Related Disorder
Author(s) -
Elise Brimble,
Christopher LeeMesser,
Péter L. Nagy,
Jennifer Propst,
Maura R.Z. Ruzhnikov
Publication year - 2018
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000492706
Subject(s) - autism spectrum disorder , neurodevelopmental disorder , intellectual disability , genetics , frameshift mutation , hypotonia , rna splicing , medicine , autism , biology , neuroscience , gene , psychiatry , exon , rna
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.