Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis
Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis
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六例中国原发性远端肾小管酸中毒儿童的突变分析和听力学评估
DOI：
10.3109/0886022x.2014.930332
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发表时间：
2014-09-01
期刊：
影响因子：
3
通讯作者：
Shao, Leping
中科院分区：
文献类型：
--
作者：
Gao, Yanxia;Xu, Yan;Shao, Leping
本研究的目的是鉴定ATP6V1B1、ATP6V0A4和SLC4A1基因突变，并评估6名来自4个不相关家庭的2 - 13岁原发性远端肾小管酸中毒儿童的听力学特征。通过直接序列分析，优先筛选ATP6V0A4和ATP6V1B1基因。如果不确定，则应分析SLC4A1基因是否突变。并对两组患者的临床特征、听力状况及内耳影像学结构进行了调查。在6例患者中鉴定出6个功能丧失突变。分别在ATP6V0A4和ATP6V1B1基因中发现了两个新的突变。ATP6V1B1基因突变的两种不同类型先证者表现为早发性重度感音神经性听力损失（SNHL）和前庭导尿管增大（EVA）。来自不同家族携带ATP6V0A4突变的2例分别表现为早发性中度混合型HL和中度SNHL，前者与EVA共病，后者无；然而，他们的两个姐姐的听力和内耳都正常。这些发现扩大了与原发性dRTA相关的ATP6V0A4和ATP6V1B1基因突变的范围。我们的研究证实了EVA与这两个基因突变的关联。需要更多的研究来阐明dRTA、SNHL、EVA与基因突变之间的关系。
The objective of this study is to identify ATP6V1B1, ATP6V0A4 and SLC4A1 genes mutations and assess audiologic characteristics in six Chinese children with primary distal renal tubular acidosis from four unrelated families between the ages of 2 and 13 years. Both ATP6V0A4 and ATP6V1B1 genes were preferentially screened in all index cases by direct sequence analysis. If inconclusive then SLC4A1 gene should be analyzed for mutation. Their clinical features, hearing status and inner ear imaging structure were also investigated. Six loss-of-function mutations were identified in six patients. Two novel mutations were identified in either of ATP6V0A4 and ATP6V1B1 genes, respectively. Two probands from different kindreds with mutations in ATP6V1B1 presented early onset profound sensorineural hearing loss (SNHL) and enlarged vestibular aqueduct (EVA). Two from different families carrying ATP6V0A4 mutations manifested early onset moderate mixed HL and moderate SNHL, respectively, the former comorbid with EVA, while the latter not; however, both their elder sisters showed normal hearing and inner ear. These findings expand the spectrum of mutations in the ATP6V0A4 and ATP6V1B1 genes associated with primary dRTA. Our study confirms the association of EVA and mutations in either of these two genes. More studies are necessary to clarify the relationship between dRTA, SNHL, EVA, and gene mutations.