Genetic Analysis of Consanguineous Pakistani Families with Congenital Stationary Night Blindness

Abstract

<b><i>Introduction:</i></b> Congenital stationary night blindness (CSNB) is a rare, largely nonprogressive, inherited retinal disorder that can be clinically classified on the basis of fundus and electroretinogram abnormalities. <b><i>Methods:</i></b> We analyzed four large consanguineous families from the Southern Punjab region of Pakistan including multiple individuals affected with CSNB. Exome sequencing was performed in probands of all four families; Sanger sequencing was performed in additional members to test co-segregation of the variants identified. <b><i>Results:</i></b> We identified two novel and likely pathogenic variants in two pedigrees, namely, NM_002905.4:c.668A&#x3e;C (p.Gln223Pro) in <i>RDH5</i> and NM_022567.2:c.908del (p.Gly303ValfsTer45) in <i>NYX</i>. In the two other families, the variants NM_002905.4:c.319G&#x3e;C (p.Gly107Arg) in <i>RDH5</i> and NM_000541.5:c.874C&#x3e;T (p.Arg292Ter) in <i>SAG</i> were identified. These latter mutations have been reported previously, but not in the Pakistani population. <b><i>Conclusions:</i></b> Our findings expand the mutational spectrum of CSNB, in particular within the population of Southern Punjab.