Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases.

TitleNovel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases.
Publication TypeJournal Article
Year of Publication2023
AuthorsHussain, HMuhammad J, Wang, M, Huang, A, Schmidt, R, Qian, X, Yang, P, Marra, M, Li, Y, Pennesi, ME, Chen, R
JournalGenes (Basel)
Volume14
Issue2
Date Published2023 Feb 09
ISSN2073-4425
KeywordsExome, Exome Sequencing, Humans, Mutation, Retinal Diseases, Whole Genome Sequencing
Abstract

Inherited retinal diseases (IRDs) are a diverse set of visual disorders that collectively represent a major cause of early-onset blindness. With the reduction in sequencing costs in recent years, whole-genome sequencing (WGS) is being used more frequently, particularly when targeted gene panels and whole-exome sequencing (WES) fail to detect pathogenic mutations in patients. In this study, we performed mutation screens using WGS for a cohort of 311 IRD patients whose mutations were undetermined. A total of nine putative pathogenic mutations in six IRD patients were identified, including six novel mutations. Among them, four were deep intronic mutations that affected mRNA splicing, while the other five affected protein-coding sequences. Our results suggested that the rate of resolution of unsolved cases via targeted gene panels and WES can be further enhanced with WGS; however, the overall improvement may be limited.

DOI10.3390/genes14020447
Alternate JournalGenes (Basel)
PubMed ID36833373
PubMed Central IDPMC9956865
Grant ListEY022356 / EY / NEI NIH HHS / United States
EY01857 / EY / NEI NIH HHS / United States
EY002520 / EY / NEI NIH HHS / United States
P30EY010572 / EY / NEI NIH HHS / United States
EY09076 / EY / NEI NIH HHS / United States
EY030499 / EY / NEI NIH HHS / United States