Identification of technically challenging variants: Whole-genome sequencing improves diagnostic yield in patients with high clinical suspicion of rare diseases.

ABSTRACT: The total burden of rare diseases is significant worldwide, with over 300 million people being affected. Many rare diseases have both well-defined clinical phenotypes and established genetic causes. However, a remarkable proportion of patients with high clinical suspicion of a rare disease remain genetically undiagnosed and stuck in the diagnostic odyssey after having a cascade of conventional genetic tests. One of the major factors contributing to this is that many types of variants are technically intractable to whole-exome sequencing (WES). In this study, the added diagnostic power of whole-genome sequencing (WGS) for patients with clinically suspected rare diseases was assessed by detecting technically challenging variants. 3,169 patients from the Hong Kong Genome Project (HKGP) were r

SUBMITTER: Ng HY 

PROVIDER: S-EPMC12269974 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature