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

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, Alan F. Wright

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)2657-2667
JournalHuman Molecular Genetics
Volume12
Issue number20
DOIs
Publication statusPublished - 15 Oct 2003

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Keywords

  • mutation
  • autosome disorder
  • blindness
  • arginine
  • heterogeneity
  • adhesions
  • bruch's basal membrane
  • collagen
  • genetic
  • molecular mass
  • photoreceptors
  • retinal degeneration
  • serine
  • age-related macular degeneration
  • retinal pigment epithelium

Cite this

Hayward, C., Shu, X., Cideciyan, A. V., Lennon, A., Barran, P., Zareparsi, S., Sawyer, L., Hendry, G., Dhillon, B., Milam, A. H., Luthert, P. J., Swaroop, A., Hastie, N. D., Jacobson, S. G., & Wright, A. F. (2003). 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. Human Molecular Genetics, 12(20), 2657-2667. https://doi.org/10.1093/hmg/ddg289