Nature Genetics
18, 174 - 176 (1998)
doi:10.1038/ng0298-174
Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with Retinitis pigmentosaStephanie A. Hagstrom1, Michael A. North2, Patsy M. Nishina3, Eliot L. Berson4
& Thaddeus P. Dryja1
1Ocular Molecular Genetics Institute and Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, Massachusetts 02114, USA.
2Sequana Therapeutics, Inc., Lajolla, California 92037, USA.
3The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
4Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, Massachusetts 02114, USA.
5e-mail: dryja@helix.mgh.harvard.edu A recessive mutation in the tub gene causes obesity, deafness and retinal degeneration in tubby mice1−4. The tub gene is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates and invertebrates4. The TULP proteins share a conserved carboxy-terminal region of approximately 200 amino-acid residues5. Here we report the analysis of the human gene TULP1, which is expressed specifically in the retina5. Upon analysing 162 patients with nonsyndromic recessive retinitis pigmentosa (RP) and 374 simplex cases of RP, we found two who were compound heterozygotes for mutations that cosegregated with disease in the respective families. Three of the mutations are missense changes affecting the conserved C-terminal region; the fourth mutation affects a splice donor site upstream of this region. Our data suggest that mutations in TULP1 are a rare cause of recessive RP and indicate that TULP1 has an essential role in the physiology of photoreceptors.
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