Department of Otolaryngology, PLA General Hospital, Beijing, People's Republic of China.
J Transl Med. 2012 May 2;10:82. doi: 10.1186/1479-5876-10-82.
Many patients with enlarged vestibular aqueduct (EVA) have either only one allelic mutant of the SLC26A4 gene or lack any detectable mutation. In this study, multiplex ligation-dependent probe amplification (MLPA) was used to screen for copy number variations (CNVs) of SLC26A4 and to reveal the pathogenic mechanisms of non-syndromic EVA (NSEVA).
Between January 2003 and March 2010, 923 Chinese patients (481 males, 442 females) with NSEVA were recruited. Among these, 68 patients (7.4%) were found to carry only one mutant allele of SLC26A4 and 39 patients (4.2%) lacked any detectable mutation in SLC26A4; these 107 patients without double mutant alleles were assigned to the patient group. Possible copy number variations in SLC26A4 were detected by SALSA MLPA.
Using GeneMapper, no significant difference was observed between the groups, as compared with the standard probe provided in the assay. The results of the capillary electrophoresis showed no significant difference between the patients and controls.
Our results suggest that CNVs and the exon deletion in SLC26A4 are not important factors in NSEVA. However, it would be premature to conclude that CNVs have no role in EVA. Genome-wide studies to explore CNVs within non-coding regions of the SLC26A4 gene and neighboring regions are warranted, to elucidate their roles in NSEVA etiology.
许多前庭水管扩大（EVA）患者仅有一个 SLC26A4 基因突变的等位基因，或缺乏任何可检测的突变。在这项研究中，多重连接依赖性探针扩增（MLPA）被用于筛选 SLC26A4 的拷贝数变异（CNVs），并揭示非综合征性 EVA（NSEVA）的发病机制。
2003 年 1 月至 2010 年 3 月，招募了 923 名中国 NSEVA 患者（481 名男性，442 名女性）。其中 68 名患者（7.4%）仅携带一个 SLC26A4 突变等位基因，39 名患者（4.2%）在 SLC26A4 中缺乏任何可检测的突变；这些 107 名无双突变等位基因的患者被分配到患者组。通过 SALSA MLPA 检测 SLC26A4 中的可能拷贝数变异。
使用 GeneMapper，与检测中提供的标准探针相比，两组之间没有观察到显著差异。毛细管电泳的结果显示患者与对照组之间没有显著差异。
我们的结果表明，SLC26A4 中的 CNVs 和外显子缺失不是 NSEVA 的重要因素。然而，要得出 CNVs 在 EVA 中没有作用的结论还为时过早。需要进行全基因组研究，以探讨 SLC26A4 基因非编码区域和邻近区域的 CNVs，阐明它们在 NSEVA 发病机制中的作用。
