title: Basal laminar drusen caused by compound heterozygous variants in the CFH gene.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, 6525 GA Nijmegen, The Netherlands.
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Marijke N
authors.initials: MN
authors.lastname: Zonneveld-Vrieling
authors.forename: Sander B
authors.initials: SB
authors.lastname: Nabuurs
authors.forename: Ellen
authors.initials: E
authors.lastname: Blokland
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D005808:Genes, Recessive / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D015593:Retinal Drusen / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA
chemical_list: C493495:CFH protein, human; D020033:Protein Isoforms; D017242:Complement Factor H