Ophthalmology in China

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Using targeted sequence capture and high throughput sequencing to detect pathogenic genes of congenital fibrosis of extraocular muscles

JIA Hong-yan1, JIAO Yong-hong1, CHANG Qing-lin2, HUA Lin3, WANG Hui1, GUO Rui1   

  1. 1. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Lab. of Ophthalmology and Visual Sciences, Beijing 100730, China; 2. Medical Imaging Center, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; 3. Department of Biomedical Information, Biomedical Engineering Institute, Capital Medical University, Beijing 100069, China
  • Received:2016-08-30 Online:2016-11-25 Published:2016-11-29
  • Contact: JIAO Yong-hong, Email: yhjiao2001@aliyun.com

Abstract:

Objective To identify the pathogenic genes of  congenital fibrosis of extraocular muscles (CFEOM) in Chinese pedigrees and sporadic patients. Design Experimental study. Participants Six Chinese families and four sporadic patients with CFEOM were enrolled. Methods Clinical data and magnetic resonance imaging (MRI) of the ocular motor nerves were collected. Genomic DNA was isolated from peripheral blood samples of family member. Mutation analyses of eleven candidate genes were performed to detect the potential mutation by using targeted exome sequencing. After bioinformatic analysis, the nucleotide substitutions of candidate genes were verified by polymerase chain reaction (PCR) and Sanger sequencing in 100 unrelated normal control individuals, then the analysis for genotype-phenotype correlation was performed. Main Outcome Measures Gene sequences. Results We identified two heterozygous KIF21A mutations c.2860C>T(p.R954W) and c.2861G>A(p.R954Q) in 80% (8/10) probands；two heterozygous TUBB3 mutations c.784C>T (p.R262C) and c.1138C>T (p.R380C) in 20%(2/10) probands. These changes were not found in normal family members and 100 normal control individuals. The patients with KIF21A mutations showed phenotypes of CFEOM1A and CFEOM3B, however the patients with TUBB3 mutations showed CFEOM3A. Conclusions KIF21A gene mutations are the leading cause of Chinese CFEOM patients. High throughput gene screening could assist clinical diagnosis and phenotyping quickly and accurately. (Ophthalmol CHN, 2016, 25: 400-404)

Key words: congenital fibrosis of extraocular muscles, KIF21A gene, TUBB3 gene