Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome.
Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome.
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DOI：
10.1186/1471-2350-14-56
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发表时间：
2013-05-24
影响因子：
--
通讯作者：
Suzuki M
中科院分区：
文献类型：
--
作者：
Ganaha A;Kaname T;Yanagi K;Naritomi K;Tono T;Usami S;Suzuki M
Pendred综合征（PS）和前庭水管扩大相关的非综合征性听力损失（伊娃）是由SLC 26 A4突变引起的。冲绳是日本列岛最西南的岛屿。据报道，来自冲绳的人和来自日本主要岛屿的人之间存在祖先差异。为了证实SLC 26 A4突变谱的种族差异，我们调查了居住在冲绳的伊娃或PS患者的SLC 26 A4突变频率和临床表现。我们研究了来自冲绳21个无关家庭的22名伊娃或PS患者。记录患者的临床病史、体格检查和耳镜检查结果、听力测试和颞骨计算机断层扫描（CT）。为了检测突变，对所有受试者的SLC 26 A4的所有21个外显子和外显子-内含子连接进行测序。使用SLC 26 A4的定量逆转录聚合酶链反应（qRT-PCR）和使用比较CT（2-ΔΔCT）方法的计算来确定与基因置换相关的致病性。22例患者中有21例发现SLC 26 A4突变。我们在9名患者（41%）中发现了IVS 15 + 5G > A/H723 R的复合杂合突变，在6名患者（27%）中发现了IVS 15 + 5G > A的纯合替换，在5名患者（23%）中发现了H723 R的纯合突变。最常见的SLC 26 A4等位基因类型为IVS 15 + 5G > A和H723 R，两者均占15/22（68%）的患者。SLC 26 A4突变类型与临床表现无明显相关性。基于qRT-PCR结果，在具有IVS 15 + 5G > A纯合置换的患者中未鉴定到SLC 26 A4的表达。SLC 26 A4的IVS 15 + 5G > A突变是冲绳PS和伊娃患者中最常见的突变。这表明，SLC 26 A4突变谱不同于日本和其他东亚国家的主要岛屿。IVS 15 + 5G > A的取代导致SLC 26 A表达的缺失，并导致PS和伊娃的表型。
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.
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DOI：
10.1016/0165-5876(95)01183-c
发表时间：
1995-07-01
影响因子：
1.5
作者：
DOWNS, MP
通讯作者：
DOWNS, MP
影响因子：
5.8
作者：
Napiontek, U;Borck, G;Pohlenz, J
通讯作者：
Pohlenz, J
DOI：
10.1016/s0165-5876(98)00123-2
发表时间：
1998-10-02
影响因子：
1.5
作者：
Cremers, CWRJ;Admiraal, RJC;Otten, BJ
通讯作者：
Otten, BJ
影响因子：
19.7
作者：
Goldfeld, M;Glaser, B;Bishara, N
通讯作者：
Bishara, N
影响因子：
1.4
作者：
JOHNSEN, T;JORGENSEN, MB;JOHNSEN, S
通讯作者：
JOHNSEN, S