A founder deletion in the TRPM1 gene associated with congenital stationary night blindness and myopia is highly prevalent in Ashkenazi Jews

Congenital stationary night blindness (CSNB) is a disease affecting the night vision of individuals. Previous studies identified TRPM1 as a gene involved in reduced night vision. Homozygous deletion of TRPM1 was the cause of CSNB in several children in 6 Ashkenazi Jewish families, thereby prompting further investigation of the carrier status within the families as well as in large cohorts of unrelated Ashkenazi and Sephardi individuals. Affected children were tested with a CSNB next-generation (NextGen) sequencing panel. A deletion of TRPM1 exons 2 through 7 was detected and confirmed by PCR and sequence analysis. A TaqMan-based assay was used to assess the frequency of this deletion in 18266 individuals of Jewish descent. High-throughput amplicon sequencing was performed on 380 samples to determine the putative deletion-flanking founder haplotype. Heterozygous TRPM1 deletions were found in 2.75% (1/36) of Ashkenazi subjects and in 1.22% (1/82) individuals of mixed Ashkenazi/Sephardic origin. The homozygous deletion frequency in our data was 0.03% (1/4025) and was only found in Ashkenazi Jewish individuals. Homozygous deletion of exons 2–7 in TRPM1 is a common cause of CSNB and myopia in many Ashkenazi Jewish patients. This deletion is a founder Ashkenazi Jewish deletion. A genetic mutation found in Ashkenazi Jewish population causes an eye disease that leads to poor vision in dim light. Yoel Hirsch and Martin M. Johansson from Dor Yeshorim, together with colleagues determined the genetic etiology of congenital stationary night blindness (CSNB) in children from six Ashkenazi families. Each affected child harbored two mutant versions of TRPM1, a gene involved in the transmission of light-elicited signals within the retina of the eye. Notably, all the children had the same large chunk of DNA missing from the gene. The researchers next screened for this genetic deletion in >18,000 individuals of Jewish descent, finding single copies of the mutation in 2.75% of Ashkenazi subjects. The findings should help doctors better diagnose CSNB and care for Jewish patients with eyesight problems.