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

被引:126
作者
Banerjee, P
Kleyn, PW
Knowles, JA
Lewis, CA
Ross, BM
Parano, E
Kovats, SG
Lee, JJ
Penchaszadeh, GK
Ott, J
Jacobson, SG
Gilliam, TC [1 ]
机构
[1] Columbia Univ Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Columbia Genome Ctr, New York, NY 10032 USA
[4] New York State Psychiat Inst, New York, NY 10032 USA
[5] Millennium Pharmaceut, Cambridge, MA 02139 USA
[6] Med Ctr, Carrabelle, FL 32322 USA
[7] Univ Catania, Pediat Clin, Catania, Italy
[8] CNR, IBFSNC, Catania, Italy
[9] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA
[10] Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA
关键词
D O I
10.1038/ng0298-177
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页码:177 / 179
页数:3
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