Huang Chun-Jui, Lei Tsun-Hsing, Chang Wei-Lun, Tu Tzong-Yang, Shiao An-Suey, Chiu Chih-Yang, Jap Tjin-Shing
Division of Endocrinology & Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Int J Pediatr Otorhinolaryngol. 2013 Sep;77(9):1495-9. doi: 10.1016/j.ijporl.2013.06.017. Epub 2013 Jul 6.
To investigate the mutations in the SLC26A4 gene in a Chinese patient with Pendred syndrome.
The diagnosis of Pendred syndrome was confirmed by the family history, pure tone audiogram, perchlorate discharge test (PDT), and computed tomography (CT) of the temporal bone. DNA extraction, PCR and DNA sequencing were performed according to standard procedures. Mutations in the SLC26A4 gene were compared with 100 unrelated subjects to exclude common polymorphism. Splice-site mutation was further confirmed by restriction enzyme length polymorphism (RFLP) with the specifically designed primers.
The proband presented with typical features of bilateral sensorineural deafness since childhood and goiter development in the early adulthood. Thyroid studies disclosed euthyroidism with elevated thyroglobulin, but negative for PDT. Marked enlargement of bilateral vestibular aqueduct (>1.5 mm) was found by CT of the temporal bone. A novel SLC26A4 splice-site mutation c.1263+1G>A (IVS10+1G>A) was identified in compound heterozygosity with the missense mutation c.1079C>T (p.A360V) in the proband. Both mutations were not found in the 100 unrelated Chinese.
Our results support previous findings that Pendred syndrome can be caused by compound heterozygous mutation in the SLC26A4 gene, in which IVS10+1G>A is a novel pathogenic mutation.
研究一名患有 Pendred 综合征的中国患者的 SLC26A4 基因突变情况。
通过家族史、纯音听力图、高氯酸盐释放试验（PDT）和颞骨计算机断层扫描（CT）确诊 Pendred 综合征。按照标准程序进行 DNA 提取、PCR 和 DNA 测序。将 SLC26A4 基因的突变与 100 名无关个体进行比较，以排除常见多态性。通过使用专门设计的引物进行限制性内切酶长度多态性（RFLP）进一步确认剪接位点突变。
先证者自幼表现出双侧感音神经性耳聋的典型特征，成年早期出现甲状腺肿。甲状腺检查显示甲状腺功能正常，甲状腺球蛋白升高，但 PDT 为阴性。颞骨 CT 发现双侧前庭导水管明显扩大（>1.5 mm）。在先证者中鉴定出一种新的 SLC26A4 剪接位点突变 c.1263+1G>A（IVS10+1G>A），与错义突变 c.1079C>T（p.A360V）呈复合杂合状态。在 100 名无关的中国人中均未发现这两种突变。
我们的结果支持先前的发现，即 Pendred 综合征可由 SLC26A4 基因的复合杂合突变引起，其中 IVS10+1G>A 是一种新的致病突变。
