Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis

Wojciech Wiszniewski, Richard Alan Lewis, David W. Stockton, Jianlan Peng, Graeme Mardon, Rui Chen, James R. Lupski

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Leber congenital amaurosis (LCA) is a clinically and genetically heterogeneous retinal dystrophy. The causes of LCA have been unraveled partially at the molecular level. At least 14 genes have been reported that, when mutated, result in LCA. To understand the roles of the known genes in LCA, a group of outbred subjects from 60 apparently either recessive families, with one or more affected individuals, or isolated patients were evaluated. One affected individual from each family underwent comprehensive mutational analysis by direct DNA sequencing of all coding regions and splice junctions of 13 LCA genes. Mutations were identified in 70% of individuals. CEP290 made the largest contribution to the identified mutations, providing 43% of those mutant alleles. We identified seven families in which affected individuals with two mutant alleles, sufficient to cause disease, had an additional mutation at a second LCA locus. Our findings suggest that mutational load can be important to penetrance of the LCA phenotype.

Original languageEnglish (US)
Pages (from-to)319-327
Number of pages9
JournalHuman genetics
Volume129
Issue number3
DOIs
StatePublished - Mar 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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