Missense mutation in the gene encoding the α subunit of rod transducin cosegregates with Nougaret's congenital night blindness

Purpose. To determine the cause of congenital stationary night blindness in the descendants of Jean Nougaret (1637-1719) from Vendémian, France. Methods. Blood samples were obtained from 12 affected and 16 unaffected relatives and used for whole genome screening. In addition, DNA samples purified from two affected members were evaluated for mutations using the single strand conformation polymorphism (SSCP) technique. The coding sequences of the following candidate genes were evaluated by SSCP analysis: rhodopsin, rhodopsin kinase, rod transducin, arrestin, rod α-phosphodiesterase (PDE), rod β-PDE, rod γ-PDE, recoverin, guanylate cyclase activating protein, the α-subunit of the cGMP-gated channel, ROM1. Variant bands were evaluated further by direct genomic sequencing and cosegregation analysis. Results. A missense change in codon 38 (exon 2) of the rod α-transducin gene was found (GGT to GAT). This mutation, designated Gly38Asp, cosegregated with the disease among all relatives evaluated. Conclusion. The perfect correlation between the Gly38Asp mutation and disease makes it highly likely that this is the cause of the Nougaret type of night blindness. A detect in the phototransduction pathway as a cause for this disease fits with previously published observations of absence of the rod a-wave seen by electroretinography.