Application of Whole Exome and Targeted Panel Sequencing in the Clinical Molecular Diagnosis of 319 Chinese Families with Inherited Retinal Dystrophy and Comparison Study

Genes
Likun WangLiping Yang

Abstract

Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases involving more than 280 genes and no less than 20 different clinical phenotypes. In this study, our aims were to identify the disease-causing gene variants of 319 Chinese patients with IRD, and compare the pros and cons of targeted panel sequencing and whole exome sequencing (WES). Patients were assigned for analysis with a hereditary eye disease enrichment panel (HEDEP) or WES examination based on time of recruitment. This HEDEP was able to capture 441 hereditary eye disease genes, which included 291 genes related to IRD. As RPGR ORF15 was difficult to capture, all samples were subjected to Sanger sequencing for this region. Among the 163 disease-causing variants identified in this study, 73 had been previously reported, and the other 90 were novel. Genes most commonly implicated in different inheritances of IRDs in this cohort were presented. HEDEP and WES achieved diagnostic yield with 41.2% and 33.0%, respectively. In addition, nine patients were found to carry pathogenic mutations in the RPGR ORF15 region with Sanger sequencing. Our study demonstrates that HEDEP can be used as a first-tier test for patients with IRDs.

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Citations

Mar 7, 2020·Ophthalmic Genetics·Mario ZanolliHernán Iturriaga
Jul 2, 2019·Investigative Ophthalmology & Visual Science·Christina Gerth-KahlertWolfgang Berger
Dec 22, 2020·Experimental Eye Research·Hualei LuoQingjiong Zhang
Mar 12, 2021·BMC Medical Genomics·Dae Joong MaHyeong Gon Yu
Feb 10, 2020·The Journal of Molecular Diagnostics : JMD·Ana Rodríguez-MuñozJosé M Millán
May 22, 2021·BMC Bioinformatics·In-Hee LeeSek Won Kong
Jun 3, 2021·International Journal of Molecular Sciences·Adrian DockeryG Jane Farrar
Jul 8, 2021·Clinical & Experimental Ophthalmology·Kathryn P Burdon
Jul 31, 2021·Frontiers in Cell and Developmental Biology·Belén García BohórquezJosé M Millán

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Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

PolyPhen
SIFT
HEDEP
GATK
Mutation Taster
GERP
WES
CoNIFER
Burrows Alignment ( BWA )
Samtools

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