Targeted long-read sequencing identifies missing pathogenic variants in unsolved Werner syndrome cases.

ABSTRACT:

Background

Werner syndrome (WS) is an autosomal recessive progeroid syndrome caused by variants in WRN. The International Registry of Werner Syndrome has identified biallelic pathogenic variants in 179/188 cases of classical WS. In the remaining nine cases, only one heterozygous pathogenic variant has been identified.

Methods

Targeted long-read sequencing (T-LRS) on an Oxford Nanopore platform was used to search for a second pathogenic variant in WRN. Previously, T-LRS was successfully used to identify missing variants and analyse complex rearrangements.

Results

We identified a second pathogenic variant in eight of nine unsolved WS cases. In five cases, T-LRS identified intronic splice variants that were confirmed by either RT-PCR or exon trapping to aff

SUBMITTER: Miller DE 

PROVIDER: S-EPMC9613861 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature