Use of genome sequencing to hunt for cryptic second-hit variants: analysis of 31 cases recruited to the 100 000 Genomes Project.

ABSTRACT:

Background

Current clinical testing methods used to uncover the genetic basis of rare disease have inherent limitations, which can lead to causative pathogenic variants being missed. Within the rare disease arm of the 100 000 Genomes Project (100kGP), families were recruited under the clinical indication 'single autosomal recessive mutation in rare disease'. These participants presented with strong clinical suspicion for a specific autosomal recessive disorder, but only one suspected pathogenic variant had been identified through standard-of-care testing. Whole genome sequencing (WGS) aimed to identify cryptic 'second-hit' variants.

Methods

To investigate the 31 families with available data that remained unsolved following formal review within the 100kGP, SVRare was used to

SUBMITTER: Moore AR 

PROVIDER: S-EPMC10715503 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature