TY - JOUR
T1 - Mutations in the CEP290 (NPHP6) gene are a frequent cause of leber congenital amaurosis
AU - Den Hollander, Anneke I.
AU - Koenekoop, Robert K.
AU - Yzer, Suzanne
AU - Lopez, Irma
AU - Arends, Maarten L.
AU - Voesenek, Krysta E.J.
AU - Zonneveld, Marijke N.
AU - Strom, Tim M.
AU - Meitinger, Thomas
AU - Brunner, Han G.
AU - Hoyng, Carel B.
AU - Van Den Born, L. Ingeborgh
AU - Rohrschneider, Klaus
AU - Cremers, Frans P.M.
N1 - Funding Information:
We thank Dr. A. de Brouwer and Dr. R. Roepman, for their helpful discussions, and C. Beumer and S. van der Velde-Visser, for excellent technical assistance. We thank all the LCA families involved and C. Robert and R. Pigeon for coordinating the visits. We are indebted to Dr. L. Carpineta, a pediatric neuroradiologist, for critically evaluating the brain CT scans and the renal ultrasounds of the proband and the affected sibling. We thank photographer C. Riopel, for the retinal photos, and Drs. I. van den Burgt and H. Kroes, for consulting on the patients. This work was supported by the Netherlands Organisation for Scientific Research (grant 916.56.160 [to A.I.d.H.]), the British Retinitis Pigmentosa Society (grant GR543 [to A.I.d.H. and F.P.M.C.]), Stichting Wetenschappelijk Onderzoek Oogziekenhuis (to L.I.v.d.B., A.I.d.H., and F.P.M.C.), the Foundation Fighting Blindness Canada (to R.K.K. and F.P.M.C.), and the Fonds de la Recherche en Santé Québec (to R.K.K.).
PY - 2006/9
Y1 - 2006/9
N2 - 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 ∼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.
AB - 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 ∼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.
UR - http://www.scopus.com/inward/record.url?scp=33748664605&partnerID=8YFLogxK
U2 - 10.1086/507318
DO - 10.1086/507318
M3 - Article
C2 - 16909394
AN - SCOPUS:33748664605
SN - 0002-9297
VL - 79
SP - 556
EP - 561
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -