Whole exome sequencing and homozygosity mapping reveals genetic defects in consanguineous Iranian families with inherited retinal dystrophies

Arash Salmaninejad; Nicola Bedoni; Zeinab Ravesh; Mathieu Quinodoz; Nasser Shoeibi; Majid Mojarrad; Alireza Pasdar; Carlo Rivolta

doi:10.1038/s41598-020-75841-9

Whole exome sequencing and homozygosity mapping reveals genetic defects in consanguineous Iranian families with inherited retinal dystrophies

Sci Rep. 2020 Nov 10;10(1):19413. doi: 10.1038/s41598-020-75841-9.

Authors

Arash Salmaninejad^{1

2}, Nicola Bedoni³, Zeinab Ravesh⁴, Mathieu Quinodoz^{4

5

6}, Nasser Shoeibi⁷, Majid Mojarrad^{1

2}, Alireza Pasdar^{8

9

10}, Carlo Rivolta^{11

12

13}

Affiliations

¹ Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
² Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Division of Genetic Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
⁴ Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
⁵ Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland.
⁶ Department of Ophthalmology, University of Basel, Basel, Switzerland.
⁷ Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
⁸ Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. pasdara@mums.ac.ir.
⁹ Medical Genetics Research Centre, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. pasdara@mums.ac.ir.
¹⁰ Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, UK. pasdara@mums.ac.ir.
¹¹ Department of Genetics and Genome Biology, University of Leicester, Leicester, UK. carlo.rivolta@iob.ch.
¹² Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland. carlo.rivolta@iob.ch.
¹³ Department of Ophthalmology, University of Basel, Basel, Switzerland. carlo.rivolta@iob.ch.

Abstract

Inherited retinal dystrophies (IRDs), displaying pronounced genetic and clinical heterogeneity, comprise of a broad range of diseases characterized by progressive retinal cell death and gradual loss of vision. By the combined use of whole exome sequencing (WES), SNP-array and WES-based homozygosity mapping, as well as directed DNA sequencing (Sanger), we have identified nine pathogenic variants in six genes (ABCA4, RPE65, MERTK, USH2A, SPATA7, TULP1) in 10 consanguineous Iranian families. Six of the nine identified variants were novel, including a putative founder mutation in ABCA4 (c.3260A>G, p.Glu1087Gly), detected in two families from Northeastern Iran. Our findings provide additional information to the molecular pathology of IRDs in Iran, hopefully contributing to better genetic counselling and patient management in the respective families from this country.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Mutational Analysis / methods
Exome Sequencing / methods*
Female
Genotype
Homozygote
Humans
Iran
Male
Mutation
Pedigree
Polymorphism, Single Nucleotide
Retinal Dystrophies / genetics*
Sequence Analysis, DNA