Mutations in a novel retina-specific gene cause autosomal dominant retinitis pigmentosa

被引:0
作者
Lori S. Sullivan
John R. Heckenlively
Sara J. Bowne
Jian Zuo
Winston A. Hide
Andreas Gal
Michael Denton
Chris F. Inglehearn
Susan H. Blanton
Stephen P. Daiger
机构
[1] Human Genetics Center,Department of Ophthalmology and Visual Science
[2] School of Public Health,Department of Developmental Neurobiology
[3] The University of Texas Health Science Center,Biochemistry Department
[4] Jules Stein Eye Institute,Department of Pediatrics
[5] University of California ,undefined
[6] St. Jude Children's Research Hospital,undefined
[7] South African National Bioinformatics Institute,undefined
[8] University of the Western Cape,undefined
[9] Institute of Human Genetics,undefined
[10] University Hospital Eppendorf ,undefined
[11] University of Otago,undefined
[12] Molecular Medicine Unit,undefined
[13] Leeds University,undefined
[14] University of Virginia,undefined
来源
Nature Genetics | 1999年 / 22卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Inherited retinal diseases are a common cause of visual impairment in children and young adults, often resulting in severe loss of vision in later life. The most frequent form of inherited retinopathy is retinitis pigmentosa (RP), with an approximate incidence of 1 in 3,500 individuals worldwide1,2. RP is characterized by night blindness and progressive degeneration of the midperipheral retina, accompanied by bone spicule-like pigmentary deposits and a reduced or absent electroretinogram (ERG). The disease process culminates in severe reduction of visual fields or blindness. RP is genetically heterogeneous, with autosomal dominant, autosomal recessive and X-linked forms. Here we have identified two mutations in a novel retina-specific gene from chromosome 8q that cause the RP1 form of autosomal dominant RP in three unrelated families. The protein encoded by this gene is 2,156 amino acids and its function is currently unknown, although the amino terminus has similarity to that of the doublecortin protein, whose gene (DCX) has been implicated in lissencephaly in humans17. Two families have a nonsense mutation in codon 677 of this gene (Arg677stop), whereas the third family has a nonsense mutation in codon 679 (Gln679stop). In one family, two individuals homozygous for the mutant gene have more severe retinal disease compared with heterozygotes.
引用
收藏
页码:255 / 259
页数:4
相关论文
共 46 条
[1]  
Banerjee P(1998) mutation in two recessive extended Dominican kindreds with autosomal recessive retinitis pigmentosa. Nature Genet 18 177-179
[2]  
Cremers FPM(1998)Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR. Hum. Mol. Genet. 7 355-362
[3]  
Dryja TP(1990)A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343 364- 366
[4]  
Dryja TP(1995)Mutations in the gene encoding the α subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa. Proc. Natl Acad. Sci. USA 92 10177- 10181
[5]  
Hagstrom SA(1998)Recessive mutations in the gene encoding the tubby-like protein TULP1 in patients with retinitis pigmentosa. Nature Genet. 18 174- 176
[6]  
North MA(1995)Autosomal recessive retinitis pigmentosa caused by mutations in the α subunit of rod cGMP phosphodiesterase. Nature Genet. 11 468-471
[7]  
Nishina PM(1991)Mutations in the human retinal degeneration slow gene in autosomal dominant retinitis pigmentosa. Nature 354 480-483
[8]  
Berson EL(1994)Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science 264 1604-1608
[9]  
Dryja TP(1998)Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene Nature Genet. 18 11-12
[10]  
Huang SH(1997). Nature Genet. 17 198-200