Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis
Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis
复制标题
内蒙古听力障碍的分子病因学：SLC26A4基因突变及相关表型分析。
DOI：
10.1186/1479-5876-6-74
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发表时间：
2008-11-30
影响因子：
7.4
通讯作者：
Wong, Lee-Jun C.
中科院分区：
文献类型：
--
作者：
Dai, Pu;Yuan, Yongyi;Wong, Lee-Jun C.
背景：中国人听力障碍的分子病因学研究尚不深入。对GJB2基因的研究发现，内蒙古地区30.4%的听力损失患者携带GJB2基因突变。本研究对SLC26A4基因突变及相关表型进行分析。方法：选择135例聋人。对111例SLC26A4基因的编码外显子进行了序列分析，其中22例携带双等位基因GJB2突变，1例携带已知的GJB2显性突变，1例携带mtDNA 1555A>；G突变。所有SLC26A4突变或变异的患者均接受高分辨率颞骨CT扫描，确诊为前庭导水管扩大和/或其他内耳畸形的患者再接受甲状腺和甲状腺激素的超声扫描。结果：发现26例SLC26A4突变患者(19.26%，26/135)。其中17例SLC26A4双等位基因突变患者经CT扫描均确诊为EVA或其他内耳畸形。9例SLC26A4杂合子突变，其中3例经CT证实为EVA或EVA合并Mondini异型增生。最常见的突变为IVS7-2A&Gt；G，占SLC26A4突变等位基因的58.14%(25/43)。20例EVA或其他内耳畸形患者中，除1例右侧甲状腺囊样改变外，其余19例经甲状腺超声检查及甲状腺激素测定证实甲状腺形态和功能正常。结论：在内蒙古中国地区，SLC26A4基因突变约占听力损失患者的12.6%。与GJB2(23/135)一起，SLC26A4是导致该区域耳聋的两个最常见的突变基因。在这个聋人群体中没有检测到彭德雷德综合症。我们建立了一种新的策略，在进行颞骨CT扫描之前检测SLC26A4突变，以发现EVA和内耳畸形患者。该模型在大规模聋人流行病学研究中具有独特的优势。
Background: The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study.Methods: One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays.Results: Twenty-six patients (19.26%, 26/135) were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed.Conclusion: In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135) of the patients with hearing loss. Together with GJB2 (23/135), SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to find EVA and inner ear malformation patients. This model has a unique advantage in epidemiologic study of large deaf population.