Xiao Yun, Luo Jianfen, Zhang Fengguo, Li Jianfeng, Han Yuechen, Zhang Daogong, Wang Mingming, Ma Yalin, Xu Lei, Bai Xiaohui, Wang Haibo
a Department of Otorhinolaryngology Head and Neck Surgery , Shandong Provincial Hospital Affiliated to Shandong University , Jinan , PR China ;
b Shandong Provincial Key Laboratory of Otology , Jinan , PR China.
Acta Otolaryngol. 2016;136(5):439-45. doi: 10.3109/00016489.2015.1132846. Epub 2016 Jan 29.
The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1.
Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1).
WS1 was diagnosed in a 4-year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis.
A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic.
PAX3基因中的新型复合杂合突变是该家族Waardenburg综合征1型（WS1）的关键遗传原因，这对WS1的分子诊断具有重要意义。
筛查一个四代中国家族性Waardenburg综合征1型（WS1）的致病突变。
根据Waardenburg综合征协会标准，对一名4岁男孩诊断为WS1。详细的家族史显示该家族中有4名患者。对该家族中4名患者和10名健康成员进行了常规临床、听力学检查和眼科评估。进行了基因分析，包括对127个已知耳聋基因进行靶向二代测序，并结合Sanger测序、TA克隆和生物信息学分析。
在PAX3基因中鉴定出一种新型复合杂合突变c.[169_170insC;172_174delAAG]（p.His57ProfsX55），该突变在中国家族中与WS1共分离。未受影响的家族成员和200名种族匹配的对照中均未发现此突变。Pax3蛋白的系统发育分析和三维（3D）建模进一步证实该新型复合杂合突变具有致病性。
