HETEROZYGOUS MISSENSE MUTATION IN THE ROD CGMP PHOSPHODIESTERASE BETA-SUBUNIT GENE IN AUTOSOMAL-DOMINANT STATIONARY NIGHT BLINDNESS

The locus for autosomal dominant congenital stationary night blindness (adCSNB) has recently been assigned to distal chromosome 4p by linkag e analysis in a large Danish family. Within the candidate gene encodin g the P-subunit of rod photoreceptor cGMP-specific phosphodiesterase ( beta PDE), we have identified a heterozygous C to A transversion in ex on 4, predicting a His258Asp change in the polypeptide. We found a per fect cosegregation (Z(max) = 22.6 at theta = 0.00) of this mutation wi th the disease phenotype suggesting that this missense mutation is res ponsible for the disease in this pedigree. Homozygous nonsense mutatio ns in the beta PDE gene have been found recently in patients with auto somal recessive retinitis pigmentosa, a common hereditary photorecepto r dystrophy.