Hoth C F, Milunsky A, Lipsky N, Sheffer R, Clarren S K, Baldwin C T
Center for Human Genetics, Boston University School of Medicine, MA 02118.
Am J Hum Genet. 1993 Mar;52(3):455-62.
Waardenburg syndrome type I (WS-I) is an autosomal dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, pigmentary disturbances, and other developmental defects. Klein-Waardenburg syndrome (WS-III) is a disorder with many of the same characteristics as WS-I and includes musculoskeletal abnormalities. We have recently reported the identification and characterization of one of the first gene defects, in the human PAX3 gene, which causes WS-I. PAX3 is a DNA-binding protein that contains a structural motif known as the paired domain and is believed to regulate the expression of other genes. In this report we describe two new mutations, in the human PAX3 gene, that are associated with WS. One mutation was found in a family with WS-I, while the other mutation was found in a family with WS-III. Both mutations were in the highly conserved paired domain of the human PAX3 gene and are similar to other mutations that cause WS. The results indicate that mutations in the PAX3 gene can cause both WS-I and WS-III.
I型瓦登伯革氏综合征（WS-I）是一种常染色体显性疾病，其特征为感音神经性听力损失、内眦异位、色素沉着紊乱及其他发育缺陷。克莱因-瓦登伯革氏综合征（WS-III）是一种具有许多与WS-I相同特征的疾病，包括肌肉骨骼异常。我们最近报告了人类PAX3基因中首个基因缺陷的鉴定与特征，该缺陷导致WS-I。PAX3是一种DNA结合蛋白，含有一个称为配对结构域的结构基序，据信它可调节其他基因的表达。在本报告中，我们描述了人类PAX3基因中与WS相关的两个新突变。一个突变在一个患有WS-I的家族中被发现，而另一个突变在一个患有WS-III的家族中被发现。这两个突变均位于人类PAX3基因高度保守的配对结构域中，且与其他导致WS的突变相似。结果表明，PAX3基因中的突变可导致WS-I和WS-III。
