Chen Hongsheng, Liao Xinbin, Liu Yalan, He Chufeng, Zhang Hua, Jiang Lu, Feng Yong, Mei Lingyun
Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2017 Aug 10;34(4):471-475. doi: 10.3760/cma.j.issn.1003-9406.2017.04.001.
To explore the pathogenetic mechanism of a family affected with Waardenburg syndrome.
Clinical data of the family was collected. Potential mutation of the MITF, SOX10 and SNAI2 genes were screened. Plasmids for wild type (WT) and mutant MITF proteins were constructed to determine their exogenous expression and subcellular distribution by Western blotting and immunofluorescence assay, respectively.
A heterozygous c.763C>T (p.R255X) mutation was detected in exon 8 of the MITF gene in the proband and all other patients from the family. No pathological mutation of the SOX10 and SNAI2 genes was detected. The DNA sequences of plasmids of MITF and mutant MITF were confirmed. Both proteins were detected with the expected size. WT MITF protein only localized in the nucleus, whereas R255X protein showed aberrant localization in the nucleus as well as the cytoplasm.
The c.763C>T mutation of the MITF gene probably underlies the disease in this family. The mutation can affect the subcellular distribution of MITF proteins in vitro, which may shed light on the molecular mechanism of Waardenburg syndrome caused by mutations of the MITF gene.
探讨一个患有瓦登伯革氏综合征（Waardenburg syndrome）家族的发病机制。
收集该家族的临床资料。筛查MITF、SOX10和SNAI2基因的潜在突变。构建野生型（WT）和突变型MITF蛋白的质粒，分别通过蛋白质免疫印迹法和免疫荧光法检测其外源表达和亚细胞分布。
在该家系的先证者及所有其他患者中，检测到MITF基因第8外显子存在杂合的c.763C>T（p.R255X）突变。未检测到SOX10和SNAI2基因的病理性突变。确认了MITF和突变型MITF质粒的DNA序列。两种蛋白均检测到预期大小。野生型MITF蛋白仅定位于细胞核，而R255X蛋白在细胞核和细胞质中均出现异常定位。
MITF基因的c.763C>T突变可能是该家族疾病的病因。该突变在体外可影响MITF蛋白的亚细胞分布，这可能为阐明MITF基因突变导致瓦登伯革氏综合征的分子机制提供线索。
