Genetic analysis of patients with retinitis pigmentosa using a cloned cDNA probe for the human gamma subunit of cyclic GMP phosphodiesterase.

We have cloned cDNAs corresponding to the human gamma subunit of retinal cyclic GMP phosphodiesterase (gamma-cGMP-PDE). The coding region of these cDNAs was identical to that reported previously by Tuteja et al. (Gene 1990, 88, 227-32). We also confirmed their assignment of gamma-cGMP-PDE to human chromosome 17. The fragment was used to search for mutations of the corresponding gamma-cGMP-PDE gene in patients with autosomal dominant, autosomal recessive, or isolate case retinitis pigmentosa, and Usher's syndrome type I. No gene deletions or rearrangements could be detected in any patient by Southern blotting. We discovered restriction fragment length polymorphisms (RFLPs) with the enzymes BstE II and EcoR I defining sets of alleles at the gamma-cGMP-PDE locus in the normal population. We used these RFLPs to analyse the genomic DNA of large sets of unrelated patients with the autosomal dominant, autosomal recessive, or isolate form of retinitis pigmentosa. Within each of these three groups, BstE II and EcoR I RFLP alleles at the gamma-cGMP-PDE locus showed no linkage disequilibrium (departure from Hardy-Weinberg equilibrium). In addition, one autosomal dominant, three autosomal recessive, and two Usher's syndrome type I pedigrees each showed no cosegregation of the gamma-cGMP-PDE locus and the disease locus. Thus, we find no evidence that mutations of the gene for the gamma subunit of cGMP phosphodiesterase are associated with the common forms of retinitis pigmentosa and Usher's syndrome type I.