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

Hafiz Muhammad Jafar Hussain, Meng Wang, Austin Huang, Ryan Schmidt, Xinye Qian, Paul Yang, Molly Marra, Yumei Li, Mark E. Pennesi, Rui Chen

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number447
JournalGenes
Volume14
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • deep intronic mutations
  • inherited retinal diseases
  • targeted gene panels
  • whole-exome sequencing
  • whole-genome sequencing (WGS)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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