A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy

被引：336

作者：

Zhang, K

Kniazeva, M

Han, M

Li, W

Yu, ZY

Yang, ZL

Li, Y

Metzker, ML

Allikmets, R

Zack, DJ

Kakuk, LE

Lagali, PS

Wong, PW

MacDonald, IM

Sieving, PA

Figueroa, DJ

Austin, CP

Gould, RJ

Ayyagari, R

Petrukhin, K ^{[1
]}

机构：

[1] Merck Res Labs, Dept Pharmacol, W Point, PA USA

[2] Merck Res Labs, Dept Human Genet, W Point, PA USA

[3] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD USA

[4] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA

[6] Univ Colorado, Howard Hughes Med Inst, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA

[7] Columbia Univ, Dept Ophthalmol, New York, NY USA

[8] Columbia Univ, Dept Pathol, New York, NY USA

[9] Univ Michigan, WK Kellogg Eye Ctr, Ann Arbor, MI 48109 USA

[10] Univ Alberta, Dept Sci Biol, Edmonton, AB, Canada

[11] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada

[12] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada

来源：

NATURE GENETICS | 2001年 / 27卷 / 01期

关键词：

D O I：

10.1038/83817

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks(1-3). Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance(1-3). Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of Very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration.

引用

页码：89 / 93

页数：5

共 30 条

[1] The effect of lipid environment and retinoids on the ATPase activity of ABCR, the photoreceptor ABC transporter responsible for Stargardt macular dystrophy [J].