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Panfeng Wang, Xueshan Xiao, Shiqiang Li, Xiaoyun Jia, Xiangming Guo, Qingjiong Zhang; New locus for autosomal dominant aniridia in a Chinese family. Invest. Ophthalmol. Vis. Sci. 2016;57(12):674.
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© ARVO (1962-2015); The Authors (2016-present)
Aniridia is a rare panocular disease characterized by noticeable iris hypoplasis and heterozygous mutations in PAX6 gene is the major cause of classic aniridia. This study aims to detect the possible pathogenic genetic cause of a Chinese aniridia family by linkage and the next generation sequencing.
A multi-generation Chinese family with autosomal dominant aniridia was ascertained. Ophthalmologic examinations were performed and a medical history was taken. The family contained 12 participating members (5 affected). Genomic DNA was prepared form venous leukocytes. A genomic wide scan was carried out using markers spaced at about 10 cM intervals for genotyping and two-point linkage was analyzed using the FASTLINK program. Whole exome and genomic sequencing were employed on chosen members (5 affected and 2 normal) to find possible mutation. Sange-dideoxy sequencing was used to verify candidate variations inside the linkage interval.
The autosomal dominant aniridia in this family mapped to two regions: D6S462 to D6S292 on chromosome 6q21, and D18S464 to D18S56 on chromosome 18q11.1. Whole exome and genomic sequencing identified a heterozygous mutation, g.12971246C>T, in 18q11.1 within the gene of SEH1L. The ESEfinder predicted that the synonymous change would destroyed exonic splicing enhancers dramatically. The potential pathogenic variant fully segregated with the disease-associated phenotype. PAX6 gene was ruled out for the aniridia in this family.
In this study, autosomal dominant aniridia was identified in a multi-generation family. Aniridia in this family was mapped to new loci on chromosome6q21 and 18q11.1. Exclusion of other regions in the genome, linkage analysis, haplotype analysis, and exome as well as genomic sequencing support 18q11.1 for autosomal dominant aniridia. This finding expand our knowledge of the molecular mechanism underlying the development of the ocular.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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