Exome sequencing of 85 Williams-Beuren syndrome cases rules out coding variation as a major contributor to remaining variance in social behavior

Molecular Genetics & Genomic Medicine
Nathan D KoppBeth A Kozel

Abstract

Large, multigenic deletions at chromosome 7q11.23 result in a highly penetrant constellation of physical and behavioral symptoms known as Williams-Beuren syndrome (WS). Of particular interest is the unusual social-cognitive profile evidenced by deficits in social cognition and communication reminiscent of autism spectrum disorders (ASD) that are juxtaposed with normal or even relatively enhanced social motivation. Interestingly, duplications in the same region also result in ASD-like phenotypes as well as social phobias. Thus, the region clearly regulates human social motivation and behavior, yet the relevant gene(s) have not been definitively identified. Here, we deeply phenotyped 85 individuals with WS and used exome sequencing to analyze common and rare variation for association with the remaining variance in social behavior as assessed by the Social Responsiveness Scale. We replicated the previously reported unusual juxtaposition of behavioral symptoms in this new patient collection, but we did not find any new alleles of large effect in the targeted analysis of the remaining copy of genes in the Williams syndrome critical region. However, we report on two nominally significant SNPs in two genes that have been implicated in...Continue Reading

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Citations

Sep 3, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Ikuo OtsukaAkitoyo Hishimoto
Aug 16, 2019·Journal of Medical Genetics·Marta Codina-SolaLuis Alberto Pérez-Jurado
Feb 21, 2021·Current Opinion in Genetics & Development·Lucy R Osborne, Carolyn B Mervis

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Methods Mentioned

BETA
gene knock out
exome sequencing
PCR
genotyping

Software Mentioned

MetaLR
Copy Caller
PLINK
VariantToBinaryPed
ANNOVAR
Bcftools
mem
SKAT
vcftools
samtools

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