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

Yoel Hirsch; David A Zeevi; Byron L Lam; Sholem Y Scher; Rachel Bringer; Bitya Cherki; Cadina C Cohen; Hagit Muallem; John Pei-Wen Chiang; Madhulatha Pantrangi; Josef Ekstein; Martin M Johansson

doi:10.1038/s41439-019-0076-4

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

Hum Genome Var. 2019 Sep 12:6:45. doi: 10.1038/s41439-019-0076-4. eCollection 2019.

Affiliations

¹ Dor Yeshorim, The Committee for Prevention of Jewish Genetic Diseases, Brooklyn, NY USA.
² Dor Yeshorim, The Committee for Prevention of Jewish Genetic Diseases, Jerusalem, Israel.
³ 3Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL USA.
⁴ Molecular Vision Laboratory, Hillsboro, OR USA.
⁵ PreventionGenetics, Marshfield, WI 54449 USA.

Abstract

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.

Keywords: Disease genetics; Rare variants.