TULP1 mutation in two extended Dominican kindreds with autosomal recessive Retinitis pigmentosa

The RP14 autosomal recessive Retinitis pigmentosa (arRP) locus has been mapped to a 2cM region of chromosome 6p21.3 (refs 1-3). TULP1 (the gene encoding tubby-like protein 1) is a candidate target for the disease mutation because it maps to the RP14 minimum genetic region and because a mutation in the highly homologous mouse tub gene leads to obesity, deafness and early progressive retinal degeneration(4-6). Here we report a splice-site mutation (IVS14+1, G-->A) that is homozygous in all affected individuals (N=33) and heterozygous in all obligate carriers (N=50) from two RP14-linked kindreds. The mutation was not observed in 210 unrelated controls. The data indicate that impairment of TULP1 protein function is a rare cause of arRP and that the normal protein plays an essential role in the physiology of the retina.