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. 2019 Aug 19;9(1):12047.
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

Alaa AlTalbishi  1   2 , Lina Zelinger  1   3 , Christina Zeitz  4 , Karen Hendler  1 , Prasanthi Namburi  1 , Isabelle Audo  4   5   6 , Ruth Sheffer  7 , Claudia Yahalom  1 , Samer Khateb  1   4 , Eyal Banin  8 , Dror Sharon  9
Affiliations

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

Alaa AlTalbishi et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Frequency of TRPM1 mutations in CSNB patients included in our study. Seventy-four percent of the patients harbor the c.880A>T mutation in a homozygous state.
Figure 2
Figure 2
The pedigree (A) and chromatogram (B) of a family with 12 affected subjects who harbor a homozygous mutation c.880A>T in the TRPM1 gene.
Figure 3
Figure 3
Clinical characteristics of patients with biallelic TRPM1 mutations. (A) Plot of cone flicker (30 Hz) response versus age correlation show very mild decline in older ages. (B) Plot of refraction versus BCVA (LogMAR) demonstrates no correlation between visual acuity and degree of myopia. Each point in the graphs represents an average of two eyes.
See this image and copyright information in PMC

References

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