Coyle B, Reardon W, Herbrick J A, Tsui L C, Gausden E, Lee J, Coffey R, Grueters A, Grossman4 A, Phelps P D, Luxon L, Kendall-Taylor P, Scherer S W, Trembath R C
Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
Hum Mol Genet. 1998 Jul;7(7):1105-12. doi: 10.1093/hmg/7.7.1105.
Pendred syndrome is an autosomal recessive disorder characterized by the association between sensorineural hearing loss and thyroid swelling or goitre and is likely to be the most common form of syndromic deafness. Within the thyroid gland of affected individuals, iodide is incompletely organified with variable effects upon thyroid hormone biosynthesis, whilst the molecular basis of the hearing loss is unknown. The PDS gene has been identified by positional cloning of chromosome 7q31, within the Pendred syndrome critical linkage interval and encodes for a putative ion transporter called pendrin. We have investigated a cohort of 56 kindreds, all with features suggestive of a diagnosis of Pendred syndrome. Molecular analysis of the PDS gene identified 47 of the 60 (78%) mutant alleles in 31 families (includes three homozygous consanguineous kindreds and one extended family segregating three mutant alleles). Moreover, four recurrent mutations accounted for 35 (74%) of PDS disease chromosomes detected and haplotype analysis would favour common founders rather than mutational hotspots within the PDS gene. Whilst these findings demonstrate molecular heterogeneity for PDS mutations associated with Pendred syndrome, this study would support the use of molecular analysis of the PDS gene in the assessment of families with congenital hearing loss.
彭德莱德综合征是一种常染色体隐性疾病，其特征为感音神经性听力损失与甲状腺肿大或甲状腺肿并存，可能是综合征性耳聋最常见的形式。在受影响个体的甲状腺内，碘化物的有机化不完全，对甲状腺激素生物合成有不同影响，而听力损失的分子基础尚不清楚。PDS基因已通过对7号染色体q31进行位置克隆而得以确定，该位置在彭德莱德综合征关键连锁区间内，编码一种名为pendrin的假定离子转运体。我们对56个家族进行了研究，所有家族均具有提示彭德莱德综合征诊断的特征。对PDS基因的分子分析在31个家族中鉴定出60个突变等位基因中的47个（78%）（包括3个纯合近亲家族和1个分离出3个突变等位基因的大家庭）。此外，4个复发性突变占检测到的PDS疾病染色体的35个（74%），单倍型分析倾向于共同的创始人而非PDS基因内的突变热点。虽然这些发现表明与彭德莱德综合征相关的PDS突变存在分子异质性，但本研究支持在评估先天性听力损失家族时使用PDS基因的分子分析。
