Homozygous tandem duplication within the gene encoding the beta-subunit of rod phosphodiesterase as a cause for autosomal recessive retinitis pigmentosa.

Autosomal recessive retinitis pigmentosa (ARRP) is a degenerative disease of photoreceptors in which defects in the rhodopsin and phosphodiesterase beta-subunit (PDEB) loci have been reported. To assess the involvement of PDEB in ARRP families from Spain, we screened a panel of 19 families for linkage to markers within or close to the PDEB gene. Homozygosity was also tested in cases of consanguinity. This combined approach ruled out PDEB as the cause of the disease in all but one of the families. Molecular characterization of the gene in that family (a consanguineous pedigree) revealed a homozygous 71-bp tandem duplication in exon 1 of the affected member, the parents being heterozygous. This defect causes a frameshift mutation which leads to a premature stop codon, suggesting that this mutant allele is the underlying cause of ARRP in this patient. According to the data presented here, the PDEB gene is not the main gene responsible for ARRP, but accounts for about 5% of the cases.