中文摘要：

目的：分析Waardenburg综合征（WS）2型家系的临床表型特征,并探讨其分子病因,为WS家系提供遗传咨询。方法：收集7个WS2型家系和散发病例（14例患者）的临床资料,分析其临床表型特征,均签署知情同意书并获取血样,提取基因组DNA,聚合酶链反应扩增MITF、SNAI2、SOX10和EDNRB基因编码区全部外显子,在ABI自动测序仪上进行正反向测序,并进行测序结果和相关数据信息的分析。结果：WS2型患者的临床表型特征最常见的是听力障碍（10/14,71.4%）、雀斑（7/14,50.0%）、虹膜异色（6/14,42.9%）和早白发（5/14,35.7%）;耳聋表型比较一致,均表现为先天性双耳极重度感音神经性聋,雀斑表型不同于国外WS患者的皮肤低色素改变。突变检测发现WS02家系MITF基因第3号外显子c.328C〉T杂合突变（p.R110X）,其他家系和散发病例均未检测到这4个基因的致病性突变。结论：WS2型患者表型特征多样,棕褐色雀斑沉着可能是国内WS患者皮肤色素异常表现的一种特殊形式。MITF基因突变R110X是导致WS02家系发病的分子病因,其他家系突变检测阴性提示存在其他未知的WS2致病基因或者拷贝数变异的可能。

英文摘要：

Objective： To investigate the clinical chacteration and molecular pathology of Waardenburg syn- drome type 2 in seven families, and provide genetic diagnosis and hereditary counseling for family members. Method：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 microphthal- mia 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 sequen- cing. Then the raw data was analyzed. Result：The most common manifestations of WS2 are sensorineuraI hearing 1oss（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 pheno- type 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 patho- logical mutation of the relevant genes （SOX10,SNAI2 and EDNRB） was detected in other pedigrees. Conclusion： There are obvious variations in clinical features of WS, while freckles may be a special subtype of cutaneous pig- ment disturbances. The MITF gene mutation, R110X,is therefore considered the disease causing mutation in pedi- gree WS02. However, there are novel disease causing genes or copy number variations in Waardenburg syndrome type 2, which require further research.