Basal Laminar Drusen Caused by Compound Heterozygous Variants in the CFH Gene

Age-related macular degeneration (AMD) is a multifactorial disease that is strongly associated with the Tyr402His variant in the complement factor H ( CFH) gene. Drusen are hallmark lesions of AMD and consist of focal-inflammatory and/or immune-mediated depositions of extracellular material at the i...

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Bibliographic Details
Published in:American journal of human genetics 2008-02, Vol.82 (2), p.516-523
Main Authors: Boon, Camiel J.F., Klevering, B. Jeroen, Hoyng, Carel B., Zonneveld-Vrieling, Marijke N., Nabuurs, Sander B., Blokland, Ellen, Cremers, Frans P.M., den Hollander, Anneke I.
Format: Article
Language:English
Subjects:
Adult
Aged
Base Sequence
Biological and medical sciences
Complement Factor H - genetics
Female
Fluorescein Angiography
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genes, Recessive - genetics
Genetics of eukaryotes. Biological and molecular evolution
Heterozygote
Humans
Inheritance Patterns - genetics
Macular Degeneration - genetics
Macular Degeneration - pathology
Male
Medical genetics
Medical sciences
Middle Aged
Models, Molecular
Molecular and cellular biology
Molecular Sequence Data
Mutation - genetics
Pedigree
Protein Isoforms - genetics
Retinal Drusen - genetics
Retinal Drusen - pathology
Sequence Analysis, DNA
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Summary:Age-related macular degeneration (AMD) is a multifactorial disease that is strongly associated with the Tyr402His variant in the complement factor H ( CFH) gene. Drusen are hallmark lesions of AMD and consist of focal-inflammatory and/or immune-mediated depositions of extracellular material at the interface of the retinal pigment epithelium (RPE) and the Bruch membrane. We evaluated the role of CFH in 30 probands with early-onset drusen and identified heterozygous nonsense, missense, and splice variants in five families. The affected individuals all carried the Tyr402His AMD risk variant on the other allele. This supports an autosomal-recessive disease model in which individuals who carry a CFH mutation on one allele and the Tyr402His variant on the other allele develop drusen. Our findings strongly suggest that monogenic inheritance of CFH variants can result in basal laminar drusen in young adults, and this can progress to maculopathy and severe vision loss later in life.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2007.11.007