Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis.
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.
den Hollander
Anneke I
AI
Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. a.denhollander@antrg.umcn.nl
Koenekoop
Robert K
RK
Yzer
Suzanne
S
Lopez
Irma
I
Arends
Maarten L
ML
Voesenek
Krysta E J
KE
Zonneveld
Marijke N
MN
Strom
Tim M
TM
Meitinger
Thomas
T
Brunner
Han G
HG
Hoyng
Carel B
CB
van den Born
L Ingeborgh
LI
Rohrschneider
Klaus
K
Cremers
Frans P M
FP
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
D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D022821:RNA Splice Sites