Genetic investigation of autosomal recessive distal renal tubular acidosis:: Evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene
Genetic investigation of autosomal recessive distal renal tubular acidosis:: Evidence for early sensorineural hearing loss associated with mutations in the ATP6V0A4 gene
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DOI：
10.1681/asn.2005121305
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发表时间：
2006-05-01
影响因子：
13.6
通讯作者：
Blanchard, Anne
中科院分区：
文献类型：
--
作者：
Vargas-Poussou, Rosa;Houillier, Pascal;Blanchard, Anne
编码顶端H+ ATP酶亚基131和4的ATP 6VIB1和ATP 6V0A4基因的突变导致隐性形式的远端肾小管酸中毒（dRTA）。ATP6V1B突变与早期感音神经性听力损失（SNHL）相关，而ATP6V0A4突变与晚发型SNHL或正常听力相关。对39例新发现的隐性dRTA家系进行了表型和基因型分析，其中18例为近亲。在31个激酶中鉴定了新的和已知的功能丧失突变。在21个家系中发现了14个新的和5个复发的ATP6V0A4基因突变。对于ATP6VIB1基因，在10个家庭中发现了两个新的和两个先前描述的突变。令人惊讶的是，7名ATP6V0A4基因突变的先证者在2个月至10岁之间发生了严重的早期SNHL。在8个家系中未发现突变。这些数据扩展了致病突变的范围，并为SNHL的遗传异质性提供了证据。这些数据还表明，这些基因中的任何一个突变都可能导致早期耳聋，并且他们强调了对独立于听力状态的隐性dRTA进行遗传筛查的重要性。
Mutations in the ATP6VIB1 and ATP6V0A4 genes, encoding subunits 131 and 4 of apical H+ ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and known loss-of-function mutations were identified in 31 kindreds. Fourteen new and five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For the ATP6VIB1 gene, two new and two previously described mutations were identified in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was detected in eight families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. The data also demonstrate that mutations in either of these genes may cause early deafness, and they highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status.