Mutations in the CEP290 (NPHP6) Gene Are a Frequent Cause of Leber Congenital Amaurosis

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2006 Aug 16

PMID 16909394

Citations 356

Authors

Anneke I den Hollander

Robert K Koenekoop

Suzanne Yzer

Irma Lopez

Maarten L Arends

Krysta E J Voesenek

Marijke N Zonneveld

Tim M Strom

Thomas Meitinger

Han G Brunner

Carel B Hoyng

L Ingeborgh van den Born

Klaus Rohrschneider

Frans P M Cremers

Affiliations

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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.

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