caa a22 4500 44586155X CHVBK 20180317145444.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00439-010-0928-y doi (NATIONALLICENCE)springer-10.1007/s00439-010-0928-y Potential involvement of more than one locus in trait manifestation for individuals with Leber congenital amaurosis [Elektronische Daten] [Wojciech Wiszniewski, Richard Lewis, David Stockton, Jianlan Peng, Graeme Mardon, Rui Chen, James Lupski] 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. Springer-Verlag, 2010 Wiszniewski Wojciech Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 604B, Houston, TX, USA aut Lewis Richard Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA aut Stockton David Department of Pediatrics and Department of Internal Medicine, Wayne State University, Detroit, MI, USA aut Peng Jianlan Human Genome Center, Baylor College of Medicine, Houston, TX, USA aut Mardon Graeme Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA aut Chen Rui Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA aut Lupski James Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 604B, Houston, TX, USA aut Human Genetics Springer-Verlag 129/3(2011-03-01), 319-327 0340-6717 129:3<319 2011 129 439 https://doi.org/10.1007/s00439-010-0928-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0928-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wiszniewski Wojciech Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 604B, Houston, TX, USA aut NATIONALLICENCE 700 1- Lewis Richard Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA aut NATIONALLICENCE 700 1- Stockton David Department of Pediatrics and Department of Internal Medicine, Wayne State University, Detroit, MI, USA aut NATIONALLICENCE 700 1- Peng Jianlan Human Genome Center, Baylor College of Medicine, Houston, TX, USA aut NATIONALLICENCE 700 1- Mardon Graeme Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA aut NATIONALLICENCE 700 1- Chen Rui Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA aut NATIONALLICENCE 700 1- Lupski James Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, 604B, Houston, TX, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/3(2011-03-01), 319-327 0340-6717 129:3<319 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer