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. 2023 Apr 22:29:1-12.
eCollection 2023.

Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry

Tamar Ben Yosef  1 , Eyal Banin  2 , Elana Chervinsky  3 , Stavit A Shalev  1   3 , Rina Leibu  4 , Eedy Mezer  1   4 , Ygal Rotenstreich  5   6   7 , Nitza Goldenberg-Cohen  1   8   9 , Shirel Weiss  9 , Muhammad Imran Khan  10 , Daan M Panneman  10 , Rebekkah J Hitti-Malin  10 , Chen Weiner  6   11 , Susanne Roosing  10 , Frans P M Cremers  10 , Eran Pras  6   11 , Dinah Zur  6   12 , Hadas Newman  6   12 , Iris Deitch  6   13 , Dror Sharon  2 , Miriam Ehrenberg  6   14
Affiliations

Genetic causes of inherited retinal diseases among Israeli Jews of Ethiopian ancestry

Tamar Ben Yosef et al. Mol Vis. .

Abstract

Purpose: This study sought to describe the phenotype frequency and genetic basis of inherited retinal diseases (IRDs) among a nationwide cohort of Israeli Jewish patients of Ethiopian ancestry.

Methods: Patients' data-including demographic, clinical, and genetic information-were obtained through members of the Israeli Inherited Retinal Disease Consortium (IIRDC). Genetic analysis was performed by either Sanger sequencing for founder mutations or next-generation sequencing (targeted next-generation sequencing or whole-exome sequencing).

Results: Forty-two patients (58% female) from 36 families were included, and their ages ranged from one year to 82 years. Their most common phenotypes were Stargardt disease (36%) and nonsyndromic retinitis pigmentosa (33%), while their most common mode of inheritance was autosomal recessive inheritance. Genetic diagnoses were ascertained for 72% of genetically analyzed patients. The most frequent gene involved was ABCA4. Overall, 16 distinct IRD mutations were identified, nine of which are novel. One of them, ABCA4-c.6077delT, is likely a founder mutation among the studied population.

Conclusions: This study is the first to describe IRDs' phenotypic and molecular characteristics in the Ethiopian Jewish community. Most of the identified variants are rare. Our findings can help caregivers with clinical and molecular diagnosis and, we hope, enable adequate therapy in the near future.

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Figures

Figure 1
Figure 1
Phenotypic and genotypic findings for the study’s cohort of Ethiopian Jewish patients with IRD. A: Phenotypic distribution. RP = retinitis pigmentosa; STGD = Stargardt disease; LCA = Leber congenital amaurosis; ACHM = achromatopsia; CRD = cone-rod dystrophy. B: Distribution of mutated genes. C: Distribution of variant types.
Figure 2
Figure 2
Novel variants identified in this study. A: Mutant (mut) and wild-type (wt) nucleotide sequence traces of the nine novel variants identified in this study. hom = homozygote; het = heterozygote. B: Evolutionary conservation of amino acids affected by three missense variants. Analysis performed with the ConSurf Server.
See this image and copyright information in PMC

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