Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis |
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| Authors: | Wojciech Wiszniewski Richard Alan Lewis Jianlan Peng Graeme Mardon James R Lupski |
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| Institution: | (1) Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 604B, Houston, TX, USA;(2) Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA;(3) Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;(4) Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA;(5) Department of Medicine, Baylor College of Medicine, Houston, TX, USA;(6) Human Genome Center, Baylor College of Medicine, Houston, TX, USA;(7) Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA;(8) Department of Pathology, Baylor College of Medicine, Houston, TX, USA;(9) Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA;(10) Texas Children’s Hospital, Houston, TX, USA;(11) Department of Pediatrics and Department of Internal Medicine, Wayne State University, Detroit, MI, USA;(12) Division of Genetic and Metabolic Disorders, Children’s Hospital of Michigan, Detroit, MI, USA; |
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| 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. |
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