Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics.

ABSTRACT:

Background

At least 50% of patients with suspected Mendelian disorders remain undiagnosed after whole-exome sequencing (WES), and the extent to which non-coding variants that are not captured by WES contribute to this fraction is unclear. Whole transcriptome sequencing is a promising supplement to WES, although empirical data on the contribution of RNA analysis to the diagnosis of Mendelian diseases on a large scale are scarce.

Results

Here, we describe our experience with transcript-deleterious variants (TDVs) based on a cohort of 5647 families with suspected Mendelian diseases. We first interrogate all families for which the respective Mendelian phenotype could be mapped to a single locus to obtain an unbiased estimate of the contribution of TDVs at 18.9%. We examine the e

SUBMITTER: Maddirevula S 

PROVIDER: S-EPMC7298854 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature