共同性外斜视家系和散发患者突变基因分析

doi:10.3760/cma.j.cn115909-20200803-00321

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摘要目的：报道一个共同性外斜视家系的新发PAX3基因突变。方法：实验研究。选取一个3代6人的共同性外斜视家系，另选择散发患者180例，正常对照组150例。提取家系成员外周血基因组DNA，使用 Illumina Hiseq 4000高通量全外显子组测序平台测序，对测序所得数据进行生物信息分析，筛选出可能的致病候选基因。针对筛选到的候选基因设计引物，在家系成员及散发患者中进行Sanger测序验证突变。结果：全外显子组测序发现PAX3基因的c.G434T突变（p.R145L）可能是共同性外斜视的致病突变。Sanger测序发现家系中2例患者均携带PAX3基因的c.434G>T杂合突变，且突变在家系中与疾病共分离，180例散发患者中有27例检测到此突变，150例正常对照者中均未发现PAX3基因G434T 突变。结论：PAX3基因的c.G434T（p.R145L）突变可能为共同性外斜视的致病突变。

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关键词 ：共同性外斜视')" href="#">

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Abstract： Objective: To report a novel mutation of the PAX3 gene in a family with concomitant exotropia. Methods: A concomitant exotropia pedigree with 6 persons over 3 generations included 2 persons from the family in this experimental study, 180 sporadic patients and 150 normal controls. The genomic DNA was extracted. Using the Illumina Hiseq 4000 high-throughput sequencing system, exome sequencing was performed, followed by a bioinformatics analysis of the sequencing results to screen out possible pathogenic candidate genes. Then the primers were designed for the selected candidate genes and Sanger sequencing was carried out to verify the mutation. Results: The mutation of the PAX3 gene c.G434T (p.R145L) was detected by exome sequencing. Both patients in the family were confirmed to carry the PAX3 c.434G>T heterozygous missense mutation by using Sanger generation sequencing. The c.434G>T heterozygous mutation of the PAX3 gene was co-segregated from concomitant exotropia in the family. The mutation was detected in 27 of 180 sporadic patients and no c.434G>T mutation in the PAX3 gene was found in 150 normal individuals who were not related to the family. Conclusions: The PAX3 gene c.434G>T (p.R145L) heterozygous missense mutation may be the pathogenic gene of concomitant exotropia.

Key words： concomitant extropia whole-exome sequencing pathogenic gene PAX3

收稿日期: 2020-08-03

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通讯作者: 刘桂香（ORCID：0000-0002-3742-6131），Email：liugx7@126.com

引用本文:

公慧敏1 周占宇1 刘桂香2. 共同性外斜视家系和散发患者突变基因分析[J]. 中华眼视光学与视觉科学杂志, 2021, 23(1): 13-18. Huimin Gong1,Zhanyu Zhou1,Guixiang Liu2. Analysis of a Gene Mutation in a Family and Sporadic Patients with Concomitant Exotropia. Chinese Journal of Optometry Ophthalmology and Visual science, 2021, 23(1): 13-18. DOI: 10.3760/cma.j.cn115909-20200803-00321

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