A clinical and molecular genetic investigation of X-linked Congenital Stationary Night Blindness
Aims: This study examines the clinical and molecular genetic features of X-linked Congenital Stationary Night Blindness (XLCSNB). The aims are to accurately document the phenotype of affected subjects by investigating functional visual deficit, to evaluate possible disease mechanisms and to confirm or refute the veracity of the "complete" and "incomplete" descriptions of phenotype in common clinical usage. In addition, by identifying causative gene mutations in the pedigrees studied, the study investigates the possibility of a genotype-phenotype correlation.;Methods: Members of fifteen families previously diagnosed as having XLCSNB underwent standardised clinical, psychophysical and electrophysiological phenotypic testing. Comprehensive mutation screening of the genes ATX and CACNAlFwas performed for each pedigree.;Results: Seven different loss-of-function mutations in the NYX gene were identified in 11 families and three mutations in the CACNA1F gene were identified in another three pedigrees. No mutations were detected in members of the remaining pedigree and this family was excluded from further study. Electrophysiological and psychophysical evidence of a functioning but impaired rod system was present in subjects from each genotype group, although scotopic responses tended to be more severely affected in subjects with NYX gene mutations. Scotopic oscillator potentials were absent in all subjects with AYXgene mutations whilst subnormal OFF responses were specific to subjects with CACNA IF gene mutations.;Conclusions: NYX gent mutations were a more frequent cause of XLCSNB than CACNA IF gene mutations in the 15 British families studied. Since evidence of a functioning rod system was identified in the majority of subjects tested, the clinical phenotypes "complete" and "incomplete" do not correlate with genotype. Instead, electrophysiological indicators of inner retinal function, specifically the characteristics of scotopic oscillatory potentials, 30Hz flicker and the OFF response may prove more discriminatory.