Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.

TitleWhole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis.
Publication TypeJournal Article
Year of Publication2011
AuthorsWang, X, Wang, H, Cao, M, Li, Z, Chen, X, Patenia, C, Gore, A, Abboud, EB, Al-Rajhi, AA, Lewis, RA, Lupski, JR, Mardon, G, Zhang, K, Muzny, D, Gibbs, RA, Chen, R
JournalHum Mutat
Date Published2011 Dec
KeywordsCalmodulin-Binding Proteins, Cell Cycle Proteins, Child, Preschool, Chromosome Mapping, Consanguinity, Cyclic Nucleotide-Gated Cation Channels, DNA Mutational Analysis, Exome, Family, Homozygote, Humans, Leber Congenital Amaurosis, Mutation, Myosin VIIa, Myosins, Pedigree, Proteins, Saudi Arabia, Sequence Analysis, DNA

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.

Alternate JournalHum Mutat
PubMed ID21901789
PubMed Central IDPMC3943164
Grant ListF32 EY019430 / EY / NEI NIH HHS / United States
F32EY19430 / EY / NEI NIH HHS / United States
R01 EY020540 / EY / NEI NIH HHS / United States
S10 RR026550 / RR / NCRR NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
R01EY018571 / EY / NEI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States

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