Expanding the Genetic Landscape of Congenital Stationary Night Blindness Through the Analysis of Consanguineous Pakistani Families.

Background/

Objectives

The current study was designed to identify the underlying genetic causes of congenital stationary night blindness (CSNB) in the indigenous consanguineous families from the Southern Punjab region of Pakistan, a population where the inherited retinal disorders are relatively common.

Methods

A detailed questionnaire and medical examination were done to check the presence of CSNB in the affected individuals of the enrolled families. Whole-exome sequencing (WES) was performed to identify the pathogenic variants, followed by segregation analyses to confirm the segregation of the identified variants with the disease phenotype in the available affected individuals of the families.

Results

We identified two novel and three known pathogenic variants in SAG, GRK1, TRPM1, SLC24A1, and GPR179, having established roles in CSNB. Two novel variants, NM_001252020.1 (p.Gly1020Arg) and NM_001004334.3 (p.Trp508Ter), were identified, and their segregation was confirmed in two families, PKIURP102 and PKIURP564, respectively. NM_002929.3 (p.Arg19Ter) and NM_001301032.1 (p.Phe538CysfsTer23) were the reported variants identified in PKIURP17 and PKIURP528 families, respectively. NM_000541.5 (p.Glu306Ter) was identified in two independent families, PKIURP552 and PKIURP565.

Conclusions

Identification of five pathogenic variants in five different genes shows the genetic heterogeneity of CSNB in Pakistani patients. Our findings also expand the mutational spectrum of CSNB in the Pakistani population and may help in the identification of mutational hotspots and may help in the genetic diagnosis of CSNB in consanguineous populations.