Cited by 191Retinal Diseases and TreatmentsRetinal Development and DisordersRetinal Imaging and Analysis

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

Hayward, Caroline, Shu, Xinhua, Cideciyan, Artur V., Lennon, Alan, Barran, Perdita, Zareparsi, Sepideh, Sawyer, Lindsay, Hendry, Grace +7 more·2003·Human Molecular Genetics

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.

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Crossref · 10.1093/hmg/ddg289

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Authors
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.
Affiliations
  • Western General Hospital (GB)
  • University of Pennsylvania (US)
  • University of Michigan (US)
  • University College London (GB)
Venue
Human Molecular Genetics
Published
2003-10-15
Volume
12
Issue
20
Pages
2657-2667
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2101414552
Cited by
191
References
30
Citations by year
2026: 4 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 6 · 2021: 11 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 6 · 2016: 10 · 2015: 7 · 2014: 13 · 2013: 5 · 2012: 14
FWCI
8.20
Type
journal article
Language
en
Open access
closed
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • ResearchOnline (Glasgow Caledonian University) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
National Eye Institute (EY-13203, EY 13729, U10EY013729, EY13385, R01EY013203, R01EY013385)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords
CTRP5, late-onset retinal degeneration, age-related macular degeneration, retinal pigment epithelium, Bruch's membrane, founder mutation, genetic heterogeneity, protein aggregation, autosomal dominant inheritance
MeSH terms
Aged, Aged, 80 and over, Aging, Amino Acid Sequence, Chromosome Mapping, Collagen, Female, Genetic Markers, Haplotypes, Humans, Immunohistochemistry, Macular Degeneration, Male, Middle Aged, Models, Genetic, Models, Molecular, Molecular Sequence Data, Mutation, Pedigree, Phenotype, Retina, Retinal Degeneration, Time Factors, Blotting, Western, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Age of Onset

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