Nonsyndromic Retinitis Pigmentosa in the Ashkenazi Jewish Population: Genetic and Clinical Aspects

Adva Kimchi, Samer Khateb, Rong Wen, Ziqiang Guan, Alexey Obolensky, Avigail Beryozkin, Shoshi Kurtzman, Anat Blumenfeld, Eran Pras, Samuel G. Jacobson, Tamar Ben-Yosef, Hadas Newman, Dror Sharon*, Eyal Banin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Purpose: To analyze the genetic and clinical findings in retinitis pigmentosa (RP) patients of Ashkenazi Jewish (AJ) descent, aiming to identify genotype–phenotype correlations. Design: Cohort study. Participants: Retinitis pigmentosa patients from 230 families of AJ origin. Methods: Sanger sequencing was performed to detect specific founder mutations known to be prevalent in the AJ population. Ophthalmologic analysis included a comprehensive clinical examination, visual acuity (VA), visual fields, electroretinography, color vision testing, and retinal imaging by OCT, pseudocolor, and autofluorescence fundus photography. Main Outcome Measures: Inheritance pattern and causative mutation; retinal function as assessed by VA, visual fields, and electroretinography results; and retinal structural changes observed on clinical funduscopy as well as by pseudocolor, autofluorescence, and OCT imaging. Results: The causative mutation was identified in 37% of families. The most prevalent RP-causing mutations are the Alu insertion (c.1297_8ins353, p.K433Rins31*) in the male germ cell-associated kinase (MAK) gene (39% of families with a known genetic cause for RP) and c.124A>G, p.K42E in dehydrodolichol diphosphate synthase (DHDDS) (33%). Additionally, disease-causing mutations were identified in 11 other genes. Analysis of clinical parameters of patients with mutations in the 2 most common RP-causing genes revealed that MAK patients had better VA and visual fields at relatively older ages in comparison with DHDDS patients. Funduscopic findings of DHDDS patients matched those of MAK patients who were 20 to 30 years older. Patients with DHDDS mutations were referred for electrophysiologic evaluation at earlier ages, and their cone responses became nondetectable at a much younger age than MAK patients. Conclusions: Our AJ cohort of RP patients is the largest reported to date and showed a substantial difference in the genetic causes of RP compared with cohorts of other populations, mainly a high rate of autosomal recessive inheritance and a unique composition of causative genes. The most common RP-causing genes in our cohort, MAK and DHDDS, were not described as major causative genes in other populations. The clinical data show that in general, patients with biallelic MAK mutations had a later age of onset and a milder retinal phenotype compared with patients with biallelic DHDDS mutations.

Original languageEnglish
Pages (from-to)725-734
Number of pages10
Issue number5
StatePublished - May 2018


FundersFunder number
National Institutes of Health
National Eye InstituteR01EY023666
Macula Vision Research Foundation
Foundation Fighting BlindnessBR-GE-0214-0639
Ministry of Health, State of Israel3-11893


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