title: Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.
abstract: 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.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors: Xia
authors: X
authors: Wang
authors: Hui
authors: H
authors: Wang
authors: Ming
authors: M
authors: Cao
authors: Zhe
authors: Z
authors: Li
authors: Xianfeng
authors: X
authors: Chen
authors: Claire
authors: C
authors: Patenia
authors: Athurva
authors: A
authors: Gore
authors: Emad B
authors: EB
authors: Abboud
authors: Ali A
authors: AA
authors: Al-Rajhi
authors: Richard A
authors: RA
authors: Lewis
authors: James R
authors: JR
authors: Lupski
authors: Graeme
authors: G
authors: Mardon
authors: Kun
authors: K
authors: Zhang
authors: Donna
authors: D
authors: Muzny
authors: Richard A
authors: RA
authors: Gibbs
authors: Rui
authors: R
authors: Chen
mesh_terms: D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005190:Family; D006720:Homozygote; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA
chemical_list: C490729:ALMS1 protein, human; C518238:CNGA3 protein, human; D002148:Calmodulin-Binding Proteins; D018797:Cell Cycle Proteins; D054815:Cyclic Nucleotide-Gated Cation Channels; C498171:IQCB1 protein, human; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D011506:Proteins; D009218:Myosins