Van Hauwe P, Everett L A, Coucke P, Scott D A, Kraft M L, Ris-Stalpers C, Bolder C, Otten B, de Vijlder J J, Dietrich N L, Ramesh A, Srisailapathy S C, Parving A, Cremers C W, Willems P J, Smith R J, Green E D, Van Camp G
Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
Hum Mol Genet. 1998 Jul;7(7):1099-104. doi: 10.1093/hmg/7.7.1099.
Pendred syndrome is an autosomal recessive disorder characterized by early childhood deafness and goiter. A century after its recognition as a syndrome by Vaughan Pendred, the disease gene ( PDS ) was mapped to chromosome 7q22-q31.1 and, recently, found to encode a putative sulfate transporter. We performed mutation analysis of the PDS gene in patients from 14 Pendred families originating from seven countries and identified all mutations. The mutations include three single base deletions, one splice site mutation and 10 missense mutations. One missense mutation (L236P) was found in a homozygous state in two consanguineous families and in a heterozygous state in five additional non-consanguineous families. Another missense mutation (T416P) was found in a homozygous state in one family and in a heterozygous state in four families. Pendred patients in three non-consanguineous families were shown to be compound heterozygotes for L236P and T416P. In total, one or both of these mutations were found in nine of the 14 families analyzed. The identification of two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome.
彭德莱德综合征是一种常染色体隐性疾病，其特征为儿童早期耳聋和甲状腺肿。在被沃恩·彭德莱德确认为一种综合征后的一个世纪，该疾病基因（PDS）被定位到7号染色体的q22 - q31.1区域，并且最近发现它编码一种假定的硫酸盐转运蛋白。我们对来自七个国家的14个彭德莱德家族的患者进行了PDS基因的突变分析，并确定了所有突变。这些突变包括三个单碱基缺失、一个剪接位点突变和十个错义突变。在两个近亲家族中发现一个错义突变（L236P）处于纯合状态，在另外五个非近亲家族中处于杂合状态。在一个家族中发现另一个错义突变（T416P）处于纯合状态，在四个家族中处于杂合状态。在三个非近亲家族中的彭德莱德患者被证明是L236P和T416P的复合杂合子。在总共分析的14个家族中，有9个家族发现了这两种突变中的一种或两种。这两种常见的PDS突变的鉴定将有助于彭德莱德综合征的分子诊断。
