Chen H S, Liao X B, Liu Y L, He C F, Zhang H, Jiang L, Feng Y, Mei L Y
Department of Otolaryngology Head and Neck Surgery,Xiangya Hospital of Central South University,Changsha.
Department of Neurosurgery,Xiangya Hospital of Central South University.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016 Dec;30(24):1946-1949. doi: 10.13201/j.issn.1001-1781.2016.24.011.
To investigate the clinical chacteration and molecular pathology of Waardenburg syndrome type 2 in seven families, and provide genetic diagnosis and hereditary counseling for family members. Clinical data of seven families with WS2（14 patients）were collected. Peripheral blood samples of the probands and related family members were collected and genomic DNA was extracted. The coding sequences of microphthalmia associated transcription factor (MITF), sex-determining region Y-box 10(SOX10), snail family zinc finger 2 (SNAI2) and endothelin receptor type B（EDNRB）were analyzed by polymerase chain reaction and DNA sequencing. Then the raw data was analyzed. The most common manifestations of WS2 are sensorineural hearing loss(10/14,71.4%), freckle(7/14, 50.0%)，heterochromia iridis(6/14, 42.9%) and premature greying(5/14,35.7%). All the deafness phenotype is congenital, bilateral profound sensorineural hearing loss. Freckles phenotype is different from cutaneous pigment abnormalities of WS in Westerners. The heterozygous mutation, c.328C>T in exon 3 of the MITF gene was detected in the proband and all patients of pedigree 2. However, no pathological mutation of the relevant genes (SOX10,SNAI2 and EDNRB) was detected in other pedigrees. There are obvious variations in clinical features of WS, while freckles may be a special subtype of cutaneous pigment disturbances. The MITF gene mutation, R110X,is therefore considered the disease causing mutation in pedigree WS02.However, there are novel disease causing genes or copy number variations in Waardenburg syndrome type 2, which require further research.
为研究7个家系的2型瓦登伯革氏综合征（WS2）的临床特征及分子病理学，并为家庭成员提供基因诊断和遗传咨询。收集了7个患有WS2的家系（14例患者）的临床资料。采集了先证者及相关家庭成员的外周血样本并提取基因组DNA。通过聚合酶链反应和DNA测序分析小眼畸形相关转录因子（MITF）、性别决定区Y框10（SOX10）、蜗牛家族锌指2（SNAI2）和内皮素B型受体（EDNRB）的编码序列。然后对原始数据进行分析。WS2最常见的表现为感音神经性听力损失（10/14，71.4%）、雀斑（7/14，50.0%）、虹膜异色症（6/14，42.9%）和早老性白发（5/14，35.7%）。所有耳聋表型均为先天性、双侧重度感音神经性听力损失。雀斑表型与西方人WS的皮肤色素异常不同。在2号家系的先证者及所有患者中检测到MITF基因第3外显子的杂合突变c.328C>T。然而，在其他家系中未检测到相关基因（SOX10、SNAI2和EDNRB）的病理性突变。WS的临床特征存在明显差异，而雀斑可能是皮肤色素紊乱的一种特殊亚型。因此，MITF基因突变R110X被认为是WS02家系的致病突变。然而，2型瓦登伯革氏综合征存在新的致病基因或拷贝数变异，需要进一步研究。
