Genetic Testing Identifies Known and Unknown Mutations in Iranian Families with Hereditary Retinal Diseases

Abstract

Purpose :
To identify the genetic basis of hereditary retinal diseases in consanguineous Iranian families

Methods :
Thirty-five unrelated Iranian families from across the country segregating progressive loss of vision were recruited following detailed ophthalmic examination. Molecular genetic tests including whole exome sequencing and homozygosity mapping were performed on all the probands. Sanger sequencing of candidate mutations was performed in all family members. Variants were analyzed using various databases and bioinformatic software.

Results : We identified 33 genomic variants in 25 previously-reported genes linked to hereditary retinal dystrophies. These mutations included: nonsense mutations in IQCB1, PRPH2, CNNM4, RDH12, SPATA7, MERTK, and CEP128; missense mutations in WDR19, WFS1, CNGA3, BBS2, BBS9, ABCA4, NMNAT1, RDH12, TULP1, RPE65, USH2A, CRB1, and RGS9, as well as frameshift mutations in RP1, SLC4A11, USH1G, GUCY2D, ALMS1 and ABCA4. Of these, 20 (60.6%) were novel. All affected individuals were homozygous for these variants except one, who was a compound heterozygote, indicating a clear effect of consanguinity in the molecular etiology of the disease. Mutations in WDR19, NMNAT1, TULP1, CEP128 and RGS9 have not been previously reported in the Iranian population.

Conclusions :
Consanguineous marriages have been widely practiced as a social norm in Iran, leading to a high prevalence of autosomal recessive disorders, including retinal degenerations. To the best of our knowledge, this is one of the largest genetic studies of Iranian families with hereditary retinal diseases. Hopefully, these data will contribute to the development of more accurate molecular tools for the diagnosis of ocular conditions in this region of the world.

This is a 2020 ARVO Annual Meeting abstract.