Nature Genetics
18, 177 - 179 (1998)
doi:10.1038/ng0298-177
TULP1 mutation in two extended Dominican kindreds with autosomal recessive Retinitis pigmentosaPoulabi Banerjee1, Patrick W. Kleyn4, James A. Knowles2, 3, Charles A. Lewis5, Barbara M. Ross2, Enrico Parano6, Steve G. Kovats4, John J. Lee4, Graciela K. Penchaszadeh2, 3, Jürg Ott7, Samuel G. Jacobson8
& T. Conrad Gilliam1, 2, 3, 9
1Departments of Genetics & Development, College of Physicians and Surgeons at Columbia University and New York State Psychiatric Institute, New York, New York 10032, USA.
2Psychiatry, College of Physicians and Surgeons at Columbia University and New York State Psychiatric Institute, New York, New York 10032, USA.
3Columbia Genome Center, College of Physicians and Surgeons at Columbia University and New York State Psychiatric Institute, New York, New York 10032, USA.
4Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA.
5Carrabelle Medical Center, Carrabelle, Florida 32322, USA.
6Pediatric Clinic, University of Catania, and IBFSNC, CNR, Catania, Italy.
7Rockefeller University, Laboratory of Statistical Genetics, New York, New York 10021, USA.
8Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
9e-mail: tcgl@columbia.edu 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 degeneration4−6. 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 RP14-1 inked 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.
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