TY - JOUR
T1 - Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
AU - Hussain, Hafiz Muhammad Jafar
AU - Wang, Meng
AU - Huang, Austin
AU - Schmidt, Ryan
AU - Qian, Xinye
AU - Yang, Paul
AU - Marra, Molly
AU - Li, Yumei
AU - Pennesi, Mark E.
AU - Chen, Rui
N1 - Funding Information:
This study was funded by the National Eye Institute (EY022356, EY018571, EY002520, P30EY010572 and EY030499), the Retinal Research Foundation, an NIH shared instrument grant (S10OD023469), the Daljit S. and Elaine Sarkaria Charitable Foundation, an Unrestricted Grant from Research to Prevent Blindness (New York), Fighting Blindness Canada, and the Vision Health Research Network.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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.
KW - deep intronic mutations
KW - inherited retinal diseases
KW - targeted gene panels
KW - whole-exome sequencing
KW - whole-genome sequencing (WGS)
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U2 - 10.3390/genes14020447
DO - 10.3390/genes14020447
M3 - Article
C2 - 36833373
AN - SCOPUS:85148890574
SN - 2073-4425
VL - 14
JO - Genes
JF - Genes
IS - 2
M1 - 447
ER -