Experimental study on using whole exome sequencing method for screening Leber congenital amaurosis in a family of candidate genes

doi:10.3877/cma.j.issn.2095-2007.2017.01.004

Abstract

Abstract:

Objective

To screen a Leber congenital amaurosis (LCA) pedigree for candidate genes and to provide the research foundation for identification of the pathogenic gene in this pedigree.

Methods

A cross-sectional study was designed. Clinical data of a Chinese family with LCA collected from Chinese Han population in Shenzhen Eye Hospital. A detailed inquiry and record all the family members with disease history, family history and obstetrical history, and conduct a comprehensive physical examination of all family members. Among them, the eye examination including visual acuity, eye position, eye movement, anterior segment examination, fundus examination, non-contact intraocular pressure, refraction, fundus photography, optical coherence tomography and electroretinogram. Venous blood genomic DNA was extracted from proband, one patients and their parents. The DNA was purified by magnetic beads extraction method. Sequencing of DNA libraries for quality detection using high-throughput sequencing platforms. Carries on the bioinformatics analysis, collects the data to carry on the standard information analysis processing, concurrently carries on the quality control examination to the data. The number of single nucleotide polymorphism and the number of deletion markers were retrieved using GATK genomic analysis network tool library. The sequencing results were annotated with SeattleSeq Annotation138, and compared with public databases of human HAPMAP, dbSNP138, Exome Sequencing Project and Exome Aggregation Consortium. The candidate genes were identified after common variants, non-coding variants and synonymous mutations were filtered out.

Results

The LCA pedigree had 3 generations and 16 family members. All patients with LCA were only in the second generation, in accordance with an autosomal recessive inheritance pattern. Seventeen candidate genes were identified, including ACTN1, C1QTNF3, FAN1, MMP28, MYO9B, NAV1, NUP62, PHLDB3, PRDM12, SLC24A4, ST3GAL3, TCIRG1, TP53, USP54, YIF1B, ZDHHC17 and ZNF107. None of these candidate genes were previously related to LCA.

Conclusions

After analyzing the DNA of the family, seventeen novel candidate genes were identified for this LCA pedigree. Our findings provided a basis for identification of the pathogenic gene in this LCA family.

Key words: Leber congenital amaurosis, Pedigree, Whole exome sequencing, Candidate pathogenic gene

Jun Zhao, Xiaosheng Huang, Shiming Peng, Tianhui Zhu, Wenling He, Yingxia Zeng, Xianming Fan, Baojian Fan. Experimental study on using whole exome sequencing method for screening Leber congenital amaurosis in a family of candidate genes[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2017, 07(01): 18-24.

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