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Whole‐exome sequencing identifies ALMS1, IQCB1, CNGA3 , and MYO7A mutations in patients with leber congenital amaurosis
Author(s) -
Wang Xia,
Wang Hui,
Cao Ming,
Li Zhe,
Chen Xianfeng,
Patenia Claire,
Gore Athurva,
Abboud Emad B.,
AlRajhi Ali A.,
A. Lewis Richard,
Lupski James R.,
Mardon Graeme,
Zhang Kun,
Muzny Donna,
Gibbs Richard A.,
Chen Rui
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21587
Subject(s) - genetics , biology , exome sequencing , disease gene identification , allele , exome , mutation , gene , phenotype , candidate gene , bioinformatics
It has been well documented that mutations in the same retinal disease gene can result in different clinical phenotypes due to difference in the mutant allele and/or genetic background. To evaluate this, a set of consanguineous patient families with Leber congenital amaurosis (LCA) that do not carry mutations in known LCA disease genes was characterized through homozygosity mapping followed by targeted exon/whole‐exome sequencing to identify genetic variations. Among these families, a total of five putative disease‐causing mutations, including four novel alleles, were found for six families. These five mutations are located in four genes, ALMS1 , IQCB1 , CNGA3 , and MYO7A . Therefore, in our LCA collection from Saudi Arabia, three of the 37 unassigned families carry mutations in retinal disease genes ALMS1 , CNGA3 , and MYO7A , which have not been previously associated with LCA, and 3 of the 37 carry novel mutations in IQCB1 , which has been recently associated with LCA. Together with other reports, our results emphasize that the molecular heterogeneity underlying LCA, and likely other retinal diseases, may be highly complex. Thus, to obtain accurate diagnosis and gain a complete picture of the disease, it is essential to sequence a larger set of retinal disease genes and combine the clinical phenotype with molecular diagnosis. 32:1450–1459, 2011. ©2011 Wiley Periodicals, Inc.