Open Collections

UBC Faculty Research and Publications

Complex Autism Spectrum Disorder in a Patient with a Novel De Novo Heterozygous MYT1L Variant Yip, Silas; Calli, Kristina; Qiao, Ying; Trost, Brett; Scherer, Stephen W.; Lewis, M. E. Suzanne

Abstract

Autism spectrum disorder (ASD) comprises a group of complex neurodevelopmental features seen in many different forms due to variable causes. Highly impactful ASD-susceptibility genes are involved in pathways associated with brain development, chromatin remodeling, and transcription regulation. In this study, we investigate a proband with complex ASD. Whole genome sequencing revealed a novel de novo missense mutation of a highly conserved amino acid residue (NP_001289981.1:p.His516Gln; chr2:1917275; hg38) in the MYT1L neural transcription factor gene. In combination with in silico analysis on gene effect and pathogenicity, we described the proband’s phenotype and made comparisons with previously reported cases to explore the spectrum of clinical features in MYT1L single nucleotide variant (SNV) cases. The phenotype–genotype correlation showed a high degree of clinical similarity with previously reported cases of missense variants in MYT1L, indicating MYT1L as the causal gene for the observed phenotype in our proband. The variant was also predicted to be damaging according to multiple in silico pathogenicity predicting tools. This study expands the clinical description of SNVs on the MYT1L gene and provides insight into its contribution to ASD.

Item Metadata

Title
Complex Autism Spectrum Disorder in a Patient with a Novel De Novo Heterozygous MYT1L Variant
Creator
Yip, Silas; Calli, Kristina; Qiao, Ying; Trost, Brett; Scherer, Stephen W.; Lewis, M. E. Suzanne
Contributor
Children's Hospital (Vancouver, B.C.). Research Institute
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2023-11-24
Description
Autism spectrum disorder (ASD) comprises a group of complex neurodevelopmental features seen in many different forms due to variable causes. Highly impactful ASD-susceptibility genes are involved in pathways associated with brain development, chromatin remodeling, and transcription regulation. In this study, we investigate a proband with complex ASD. Whole genome sequencing revealed a novel de novo missense mutation of a highly conserved amino acid residue (NP_001289981.1:p.His516Gln; chr2:1917275; hg38) in the MYT1L neural transcription factor gene. In combination with in silico analysis on gene effect and pathogenicity, we described the proband’s phenotype and made comparisons with previously reported cases to explore the spectrum of clinical features in MYT1L single nucleotide variant (SNV) cases. The phenotype–genotype correlation showed a high degree of clinical similarity with previously reported cases of missense variants in MYT1L, indicating MYT1L as the causal gene for the observed phenotype in our proband. The variant was also predicted to be damaging according to multiple in silico pathogenicity predicting tools. This study expands the clinical description of SNVs on the MYT1L gene and provides insight into its contribution to ASD.
Subject
MYT1L; autism spectrum disorder (ASD); neurodevelopmental disorder; single nucleotide variant (SNV); de novo; whole genome sequencing (WGS)
Genre
Article
Type
Text
Language
eng
Date Available
2024-03-12
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0440659
URI
http://hdl.handle.net/2429/87563
Affiliation
Medical Genetics, Department of
Citation
Genes 14 (12): 2122 (2023)
Publisher DOI
10.3390/genes14122122
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher
Rights URI
https://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository
DSpace

Item Media

Item Citations and Data

Rights

CC BY 4.0