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

Hum Genet. 2011 Mar;129(3):319-27. doi: 10.1007/s00439-010-0928-y. Epub 2010 Dec 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics
  • Cell Cycle Proteins
  • Cohort Studies
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Eye Proteins / genetics
  • Genetic Loci*
  • Humans
  • Leber Congenital Amaurosis / genetics*
  • Multifactorial Inheritance / genetics*
  • Neoplasm Proteins / genetics
  • Pedigree
  • Penetrance
  • Quantitative Trait, Heritable*


  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Eye Proteins
  • Neoplasm Proteins