TULP1 MUTATION IN 2 EXTENDED DOMINICAN KINDREDS WITH AUTOSOMAL RECESSIVE RETINITIS-PIGMENTOSA

The RP14 autosomal recessive Retinitis pigmentosa (arRP) locus has bee n mapped to a 2cM region of chromosome 6p21.3 (refs 1-3). TULP1 (the g ene encoding tubby-like protein 1) is a candidate target for the disea se mutation because it maps to the RP14 minimum genetic region and bec ause a mutation in the highly homologous mouse tub gene leads to obesi ty, deafness and early progressive retinal degeneration(4-6). Here we report a splice-site mutation (IVS14+1, G-->A) that is homozygous in a ll affected individuals (N=33) and heterozygous in all obligate carrie rs (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.