TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations

Alaa AlTalbishi; Lina Zelinger; Christina Zeitz; Karen Hendler; Prasanthi Namburi; Isabelle Audo; Ruth Sheffer; Claudia Yahalom; Samer Khateb; Eyal Banin; Dror Sharon

doi:10.1038/s41598-019-46811-7

TRPM1 Mutations are the Most Common Cause of Autosomal Recessive Congenital Stationary Night Blindness (CSNB) in the Palestinian and Israeli Populations

Sci Rep. 2019 Aug 19;9(1):12047. doi: 10.1038/s41598-019-46811-7.

Authors

Alaa AlTalbishi^{1

2}, Lina Zelinger^{1

3}, Christina Zeitz⁴, Karen Hendler¹, Prasanthi Namburi¹, Isabelle Audo^{4

5

6}, Ruth Sheffer⁷, Claudia Yahalom¹, Samer Khateb^{1

4}, Eyal Banin⁸, Dror Sharon⁹

Affiliations

¹ Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
² St. John of Jerusalem Eye Hospital Group, East Jerusalem, 91198, Palestine.
³ Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute, NIH, Bathesda, MD 20892, United States.
⁴ Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, France.
⁵ CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DGOS CIC 1423, Paris, France.
⁶ Institute of Ophthalmology, University College of London, London, UK.
⁷ Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, 91120, Jerusalem, Israel.
⁸ Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel. [email protected].
⁹ Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel. [email protected].

Abstract

Precise genetic and phenotypic characterization of congenital stationary night blindness (CSNB) patients is needed for future therapeutic interventions. The aim of this study was to estimate the prevalence of CSNB in our populations and to study clinical and genetic aspects of the autosomal recessive (AR) form of CSNB. This is a retrospective cohort study of Palestinian and Israeli CSNB patients harboring mutations in TRPM1 underwent comprehensive ocular examination. Genetic analysis was performed using homozygosity mapping and sequencing. 161 patients (from 76 families) were recruited for this study, leading to a prevalence of 1:6210 in the vicinity of Jerusalem, much higher than the worldwide prevalence. 61% of the families were consanguineous with AR inheritance pattern. Biallelic pathogenic TRPM1 mutations were identified in 36 families (72 patients). Two founder mutations explain the vast majority of cases: a nonsense mutation c.880A>T (p.Lys294*) identified in 22 Palestinian families and a large genomic deletion (36,445 bp) encompassing exons 2-7 of TRPM1 present in 13 Ashkenazi Jewish families. Most patients were myopic (with mean BCVA of 0.40 LogMAR) and all had absent rod responses in full field electroretinography. To the best of our knowledge, this is the largest report of a clinical and genetic analysis of patients affected with CSNB due to TRPM1 mutations.

Publication types

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

MeSH terms

Alleles
Arabs
Eye Diseases, Hereditary / diagnosis
Eye Diseases, Hereditary / genetics*
Female
Genes, Recessive*
Genetic Association Studies* / methods
Genetic Diseases, X-Linked / diagnosis
Genetic Diseases, X-Linked / genetics*
Genetic Predisposition to Disease*
Genotype
Humans
Jews
Male
Mutation*
Myopia / diagnosis
Myopia / genetics*
Night Blindness / diagnosis
Night Blindness / genetics*
Pedigree
Phenotype
TRPM Cation Channels / genetics*

Substances

TRPM Cation Channels
TRPM1 protein, human

Supplementary concepts

Night blindness, congenital stationary