Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct:: a unique spectrum of mutations in Japanese
Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct:: a unique spectrum of mutations in Japanese
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DOI：
10.1038/sj.ejhg.5201073
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发表时间：
2003-12-01
影响因子：
5.2
通讯作者：
Usami, S
中科院分区：
文献类型：
--
作者：
Tsukamoto, K;Suzuki, H;Usami, S
分子诊断对精确诊断、亚分类、预后和治疗选择做出了重大贡献。已知 PDS (SLC26A4) 基因突变导致 Pendred 综合征和与前庭导水管扩大相关的非综合征性听力损失，PDS 基因的分子确认在这些疾病的诊断中变得非常重要。在本研究中，PDS 突变分析证实，PDS 突变存在于 90% 的 Pendred 家族中，以及 78.1% 的与前庭导水管扩大相关的非综合征性听力损失家族中。此外，相同突变组合导致的不同表型表达表明这两种病症是连续类别疾病的一部分。有趣的是，日本人的 PDS 突变谱（包括本研究揭示的 7 个新突变）与白种人中发现的 PDS 突变谱有很大不同。在检测到的新突变中，53% 是 H723R 突变，这表明可能存在创始人效应。因此，种族背景可能很重要，在进行基因检测时应注意这一点。日本人的PDS基因突变谱可能具有东亚人群的代表性，其阐明有望促进多种疾病的分子诊断。
Molecular diagnosis makes a substantial contribution to precise diagnosis, subclassification, prognosis, and selection of therapy. Mutations in the PDS (SLC26A4) gene are known to be responsible for both Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, and the molecular confirmation of the PDS gene has become important in the diagnosis of these conditions. In the present study, PDS mutation analysis confirmed that PDS mutations were present and significantly responsible in 90% of Pendred families, and in 78.1% of families with nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Furthermore, variable phenotypic expression by the same combination of mutations indicated that these two conditions are part of a continuous category of disease. Interestingly, the PDS mutation spectrum in Japanese, including the seven novel mutations revealed by this study, is very different from that found in Caucasians. Of the novel mutations detected, 53% were the H723R mutation, suggesting a possible founder effect. Ethnic background is therefore presumably important and should be noted when genetic testing is being performed. The PDS gene mutation spectrum in Japanese may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of a variety of diseases.