Journal Article

Mutation in a short-chain collagen gene, <i>CTRP5</i>, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration

Caroline Hayward, Xinhua Shu, Artur V. Cideciyan, Alan Lennon, Perdita Barran, Sepideh Zareparsi, Lindsay Sawyer, Grace Hendry, Baljean Dhillon, Ann H. Milam, Philip J. Luthert, Anand Swaroop, Nicholas D. Hastie, Samuel G. Jacobson and Alan F. Wright

in Human Molecular Genetics

Volume 12, issue 20, pages 2657-2667
Published in print October 2003 | ISSN: 0964-6906
Published online October 2003 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddg289
Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration

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A primary feature of age-related macular degeneration (AMD) is the presence of extracellular deposits between the retinal pigment epithelium (RPE) and underlying Bruch's membrane, leading to RPE dysfunction, photoreceptor death and severe visual loss. AMD accounts for about 50% of blind registrations in Western countries and is a common, genetically complex disorder. Very little is known regarding its molecular basis. Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder with striking clinical and pathological similarity to AMD. Here we show that L-ORD is genetically heterogeneous and that a proposed founder mutation in the CTRP5 (C1QTNF5) gene, which encodes a novel short-chain collagen, changes a highly conserved serine to arginine (Ser163Arg) in 7/14 L-ORD families and 0/1000 control individuals. The mutation occurs in the gC1q domain of CTRP5 and results in abnormal high molecular weight aggregate formation which may alter its higher-order structure and interactions. These results indicate a novel disease mechanism involving abnormal adhesion between RPE and Bruch's membrane.

Journal Article.  6504 words.  Illustrated.

Subjects: Genetics and Genomics

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