Rare variants in the genetic background modulate cognitive and developmental phenotypes in individuals carrying disease-associated variants.

ABSTRACT:

Purpose

To assess the contribution of rare variants in the genetic background toward variability of neurodevelopmental phenotypes in individuals with rare copy-number variants (CNVs) and gene-disruptive variants.

Methods

We analyzed quantitative clinical information, exome sequencing, and microarray data from 757 probands and 233 parents and siblings who carry disease-associated variants.

Results

The number of rare likely deleterious variants in functionally intolerant genes ("other hits") correlated with expression of neurodevelopmental phenotypes in probands with 16p12.1 deletion (n=23, p=0.004) and in autism probands carrying gene-disruptive variants (n=184, p=0.03) compared with their carrier family members. Probands with 16p12.1 deletion and a strong family histo

SUBMITTER: Pizzo L 

PROVIDER: S-EPMC6405313 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature