Gong Hui-Min, Wang Jing, Xu Jing, Zhou Zhan-Yu, Li Jing-Wen, Chen Shu-Fang
Ophthalmologic Center, Qingdao Municipal Hospital, the Affiliated Municipal Hospital of Qingdao University, Qingdao 266000, Shandong Province, China.
Department of Ophthalmology, Dezhou People's Hospital, Dezhou 253000, Shandong Province, China.
Int J Ophthalmol. 2017 Aug 18;10(8):1223-1228. doi: 10.18240/ijo.2017.08.06. eCollection 2017.
To identify the potentially pathogenic gene variants that contributes to the etiology of strabismus.
A Chinese pedigree with strabismus was collected and the exomes of two affected individuals were sequenced using the next-generation sequencing technology. The resulting variants from exome sequencing were filtered by subsequent bioinformatics methods and the candidate mutation was verified as heterozygous in the affected proposita and her mother by sanger sequencing.
Whole exome sequencing and filtering identified a nonsynonymous mutation c.434G-T transition in paired box 3 (PAX3) in the two affected individuals, which were predicted to be deleterious by more than 4 bioinformatics programs. This altered amino acid residue was located in the conserved PAX domain of PAX3. This gene encodes a member of the PAX family of transcription factors, which play critical roles during fetal development. Mutations in PAX3 were associated with Waardenburg syndrome with strabismus.
Our results report that the c.434G-T mutation (p.R145L) in PAX3 may contribute to strabismus, expanding our understanding of the causally relevant genes for this disorder.
鉴定导致斜视病因的潜在致病基因变异。
收集一个患有斜视的中国家系，使用二代测序技术对两名患病个体的外显子组进行测序。通过后续生物信息学方法筛选外显子组测序产生的变异，通过桑格测序验证候选突变在患病先证者及其母亲中为杂合子。
全外显子组测序和筛选在两名患病个体中鉴定出成对盒基因3（PAX3）中的一个非同义突变c.434G-T转换，超过4个生物信息学程序预测该突变有害。这种改变的氨基酸残基位于PAX3的保守PAX结构域中。该基因编码转录因子PAX家族的一个成员，其在胎儿发育过程中起关键作用。PAX3突变与伴有斜视的瓦登伯革氏综合征相关。
我们的结果表明PAX3中的c.434G-T突变（p.R145L）可能导致斜视，扩展了我们对该疾病相关致病基因的理解。
