Department of Otorhinolaryngology-Head and Neck Surgery, University of the Ryukyus, Okinawa, Japan.
BMC Med Genet. 2013 May 24;14:56. doi: 10.1186/1471-2350-14-56.
Pendred syndrome (PS) and nonsyndromic hearing loss associated with enlarged vestibular aqueduct (EVA) are caused by SLC26A4 mutations. The Okinawa Islands are the southwestern-most islands of the Japanese archipelago. And ancestral differences have been reported between people from Okinawa Island and those from the main islands of Japan. To confirm the ethnic variation of the spectrum of SLC26A4 mutations, we investigated the frequencies of SLC26A4 mutations and clinical manifestations of patients with EVA or PS living in the Okinawa Islands.
We examined 22 patients with EVA or PS from 21 unrelated families in Okinawa Islands. The patient's clinical history, findings of physical and otoscopic examinations, hearing test, and computed tomography (CT) scan of the temporal bones were recorded. To detect mutations, all 21 exons and the exon-intron junctions of SLC26A4 were sequenced for all subjects. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) for SLC26A4 and calculations using the comparative CT (2(-ΔΔCT)) method were used to determine the pathogenicity associated with gene substitutions.
SLC26A4 mutations were identified in 21 of the 22 patients. We found a compound heterozygous mutation for IVS15 + 5G > A/H723R in nine patients (41%), a homozygous substitution of IVS15 + 5G > A in six patients (27%), and homozygous mutation for H723R in five patients (23%). The most prevalent types of SLC26A4 alleles were IVS15 + 5G > A and H723R, which both accounted for 15/22 (68%) of the patients. There were no significant correlations between the types of SLC26A4 mutation and clinical manifestations. Based on qRT-PCR results, expression of SLC26A4 was not identified in patients with the homozygous substitution of IVS15 + 5G > A.
The substitution of IVS15 + 5G > A in SLC26A4 was the most common mutation in uniquely found in patients with PS and EVA in Okinawa Islands. This suggested that the spectrum of SLC26A4 mutation differed from main islands of Japan and other East Asian countries. The substitution of IVS15 + 5G > A leads to a loss of SLC26A expression and results in a phenotype of PS and EVA.
Pendred 综合征（PS）和伴有扩大的前庭水管（EVA）的非综合征性听力损失是由 SLC26A4 突变引起的。冲绳群岛是日本列岛最西南的岛屿。人们已经报道了冲绳岛居民和日本主岛居民之间存在祖先差异。为了确认 SLC26A4 突变谱的种族变异，我们调查了生活在冲绳群岛的 EVA 或 PS 患者的 SLC26A4 突变的频率和临床表现。
我们检查了来自 21 个无关家庭的 22 名患有 EVA 或 PS 的患者。记录了患者的临床病史、体格检查和耳镜检查结果、听力测试和颞骨 CT 扫描。为了检测突变，对所有 21 个外显子和 SLC26A4 的外显子-内含子接头进行了测序。使用定量逆转录聚合酶链反应（qRT-PCR）对 SLC26A4 进行检测，并使用比较 CT（2(-ΔΔCT)）方法计算与基因替换相关的致病性。
在 22 名患者中的 21 名中发现了 SLC26A4 突变。我们在 9 名患者（41%）中发现了 IVS15+5G>A/H723R 的复合杂合突变，在 6 名患者（27%）中发现了 IVS15+5G>A 的纯合突变，在 5 名患者（23%）中发现了 H723R 的纯合突变。最常见的 SLC26A4 等位基因类型是 IVS15+5G>A 和 H723R，它们在 22 名患者中均占 15/22（68%）。SLC26A4 突变的类型与临床表现之间没有显著的相关性。根据 qRT-PCR 结果，在 IVS15+5G>A 的纯合子替换患者中未检测到 SLC26A4 的表达。
在冲绳群岛发现的 PS 和 EVA 患者中，SLC26A4 的 IVS15+5G>A 替换是最常见的突变。这表明 SLC26A4 突变谱与日本主岛和其他东亚国家不同。IVS15+5G>A 的替换导致 SLC26A 的表达缺失，并导致 PS 和 EVA 的表型。
