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

Molecular Syndromology
Elise BrimbleMaura R Z Ruzhnikov

Abstract

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.

References

Jan 28, 2005·The European Journal of Neuroscience·Karen PorterSeth G N Grant
Mar 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Gavin RumbaughRichard L Huganir
Jan 16, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xiaochuan GuoGavin Rumbaugh
Apr 3, 2009·Nucleic Acids Research·François-Olivier DesmetChristophe Béroud
Jun 21, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·James P ClementGavin Rumbaugh
Jan 24, 2015·Science·Mathias UhlénFredrik Pontén
Feb 19, 2015·Nature Biotechnology·Mihaela PerteaSteven L Salzberg
Mar 10, 2015·Nature Methods·Daehwan KimSteven L Salzberg
Jun 17, 2015·American Journal of Medical Genetics. Part a·Michael J ParkerDavid R FitzPatrick
Mar 19, 2016·Journal of Medical Genetics·Cyril MignotChristel Depienne
Jul 20, 2017·Epileptic Disorders : International Epilepsy Journal with Videotape·Tetsuya OkazakiYoshihiro Maegaki
Dec 20, 2017·Molecular and Cellular Neurosciences·Robert S PorterShigeki Iwase

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