RECESSIVE MUTATIONS IN THE GENE ENCODING THE TUBBY-LIKE PROTEIN TULP1IN PATIENTS WITH RETINITIS-PIGMENTOSA

A recessive mutation in the tub gene causes obesity, deafness and reti nal degeneration in tubby mice(1-4). The tub gene is a member of a fam ily of tubby-like genes (TULPs) that encode proteins of unknown functi on. Members of this family have been identified in plants, vertebrates and invertebrates(4). The TULP proteins share a conserved carboxy-ter minal region of approximately 200 amino-acid residues(5). Here we repo rt the analysis of the human gene TULP?, which is expressed specifical ly in the retina(5). Upon analysing 162 patients with nonsyndromic rec essive retinitis pigmentosa (RP) and 374 simplex cases of RP, we found two who were compound heterozygotes for mutations that cosegregated w ith disease in the respective families. Three of the mutations are mis sense changes affecting the conserved C-terminal region; the fourth mu tation affects a splice donor site upstream of this region. Our data s uggest that mutations in TULP1 are a rare cause of recessive RP and in dicate that TULP1 has an essential role in the physiology of photorece ptors.