Nature 354, 478 - 480 (12 December 1991); doi:10.1038/354478a0

A three-base-pair deletion in the peripherin–RDS gene in one form of retinitis pigmentosa

G. Jane Farrar, Paul Kenna, Siobhán A. Jordan, Rajendra Kumar-Singh, Marian M. Humphries, Elizabeth M. Sharp, Denise M. Sheils & Peter Humphries

Department of Genetics, Trinity College Dublin, Lincoln Place Gate, Dublin 2, Ireland

THE group of retinopathies termed retinitis pigmentosa (RP) greatly contribute to visual dysfunction in man with a frequency of roughly 1 in 4,000 (refs 1, 2). We mapped the first autosomal dominant RP (adRP) gene to chromosome 3q (refs 3, 4), close to the gene encoding rhodopsin, a rod photoreceptor pigment protein. Subsequently, mutations in this gene have been implicated as responsible for some forms of adRP^5–9. Another adRP gene has been mapped to chromosome 8p (ref. ¹⁰). A third adRP gene in a large Irish pedigree has been mapped to chromosome 6p (refs 11,12), showing tight linkage with the gene for peripherin^13,14, a photoreceptor cell-specific glycoprotein, which is thus a strong candidate for the defective gene. We have now identified a three-base-pair deletion which results in the loss of one of a pair of highly conserved cysteine residues in the predicted third transmem-brane domain of peripherin. This deletion segregates with the disease phenotype but is not present in unaffected controls, and suggests that mutant peripherin gives rise to retinitis pigmentosa.

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