title: Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis.
abstract: Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for approximately 45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation (c.2991+1655A-->G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. a.denhollander@antrg.umcn.nl
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: Suzanne
authors.initials: S
authors.lastname: Yzer
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Arends
authors.forename: Krysta E J
authors.initials: KE
authors.lastname: Voesenek
authors.forename: Marijke N
authors.initials: MN
authors.lastname: Zonneveld
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohrschneider
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D000951:Antigens, Neoplasm / Q000235:genetics*; D018797:Cell Cycle Proteins; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D005091:Exons / Q000235:genetics; D006720:Homozygote; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D022821:RNA Splice Sites / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D022821:RNA Splice Sites