Borck Guntram, Roth Christian, Martiné Ursula, Wildhardt Gabriele, Pohlenz Joachim
Children's Hospital, Johannes-Gutenberg-University of Mainz, D-55101 Mainz.
J Clin Endocrinol Metab. 2003 Jun;88(6):2916-21. doi: 10.1210/jc.2002-021334.
Pendred's syndrome, an autosomal-recessive condition characterized by congenital sensorineural hearing loss and goiter, is caused by mutations in the PDS gene. Located on chromosome 7q22-q31, it encodes a chloride-iodide transporter expressed in the thyroid, inner ear, and kidney. We investigated the PDS gene of six affected individuals from four unrelated families with Pendred's syndrome by direct sequencing. PDS mutations were identified in homozygous or compound heterozygous state in all six cases. A homozygous missense mutation leading to the amino acid substitution S133T was detected in a family of Turkish origin. The mutations found in the other affected individuals, who originate from Germany, were V138F/Y530H, V138F/E384G, and V138F/V138F. Because V138F was found in the German patients with Pendred's syndrome on at least one allele, we genotyped five microsatellite markers located in the PDS region. All affected German individuals shared a common haplotype at three microsatellite markers located close to or within the PDS gene. We therefore concluded that V138F is a founder mutation in our cohort of German families with Pendred's syndrome.
彭德莱德综合征是一种常染色体隐性疾病，其特征为先天性感音神经性听力损失和甲状腺肿，由PDS基因突变引起。该基因位于7号染色体的7q22 - q31区域，编码一种在甲状腺、内耳和肾脏中表达的氯碘转运体。我们通过直接测序研究了来自四个不相关家族的六名患有彭德莱德综合征的患者的PDS基因。在所有六个病例中均鉴定出处于纯合或复合杂合状态的PDS突变。在一个土耳其裔家族中检测到一个导致氨基酸替换S133T的纯合错义突变。在其他来自德国的受影响个体中发现的突变是V138F/Y530H、V138F/E384G和V138F/V138F。由于在患有彭德莱德综合征的德国患者中至少有一个等位基因上发现了V138F，我们对位于PDS区域的五个微卫星标记进行了基因分型。所有受影响的德国个体在位于PDS基因附近或内部的三个微卫星标记上共享一个常见单倍型。因此，我们得出结论，V138F是我们德国彭德莱德综合征家族队列中的一个奠基者突变。
