Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa

Scientific Reports
Raquel Perez-CarroCarmen Ayuso

Abstract

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis.

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Citations

Sep 9, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Caroline Van CauwenberghElfride De Baere
May 17, 2017·Human Molecular Genetics·G Jane FarrarPete Humphries
Aug 12, 2017·PloS One·Sheila Castro-SánchezDiana Valverde
May 26, 2018·JAMA Ophthalmology·Peter Charbel IssaThomas Hummel
May 1, 2021·BMC Ophthalmology·Asif Naveed AhmedShamim Saleha
Jun 3, 2021·International Journal of Molecular Sciences·Adrian DockeryG Jane Farrar

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Methods Mentioned

BETA
genotyping
PCR
Illumina Sequencing

Software Mentioned

Analyzer Splice Tool
Agilent CytoGenomics
Genome Analysis Toolkit ( GATK )
ENSEMBL Variant Effect Predictor
Coffalyser
UCSC browser
VariantStudio Variant Analysis
DNAnexus
Illumina RTA
. Net

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