Novel Mutations in the SCNN1A Gene Causing Pseudohypoaldosteronism Type 1
Novel Mutations in the SCNN1A Gene Causing Pseudohypoaldosteronism Type 1
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DOI：
10.1371/journal.pone.0065676
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发表时间：
2013-06-06
期刊：
影响因子：
3.7
通讯作者：
Fu, Qihua
中科院分区：
文献类型：
--
作者：
Wang, Jian;Yu, Tingting;Fu, Qihua
假性醛固酮减少症1型(PHA1)是一种罕见的遗传性疾病，其特征是对醛固酮的作用产生抵抗。上皮性钠通道(ENaC)亚单位基因(SCNN1A、SCNN1B、SCNN1G)和编码盐皮质激素受体的NR3C2基因突变分别导致全身性PHA1和肾脏PHA1。PHA1的常见临床表现包括盐耗、高钾血症、代谢性酸中毒和新生儿期血浆醛固酮水平升高。在这项研究中，我们描述了两名中国系统性PHA1患者的临床和生化表现。对SCNN1A基因进行序列分析，发现1例患者存在复合杂合突变(c.1311delG和c.1439+1G>；C)，另1例患者存在纯合子突变(c.814_815insG)，三种突变均为新发现。对微型基因结构中剪接模式的进一步分析表明，c.1439+1G>；C突变可以导致内含子9的保留，因为5‘-供体剪接位点在转录后处理过程中消失。总之，我们的研究在两名中国系统性PHA1患者中发现了三个新的SCNN1A基因突变。
Pseudohypoaldosteronism type 1 (PHA1) is a rare inherited disease characterized by resistance to the actions of aldosterone. Mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G) of the epithelial sodium channel (ENaC) and the NR3C2 gene encoding the mineralocorticoid receptor, result in systemic PHA1 and renal PHA1 respectively. Common clinical manifestations of PHA1 include salt wasting, hyperkalaemia, metabolic acidosis and elevated plasma aldosterone levels in the neonatal period. In this study, we describe the clinical and biochemical manifestations in two Chinese patients with systemic PHA1. Sequence analysis of the SCNN1A gene revealed a compound heterozygous mutation (c.1311delG and c. 1439+1G>C) in one patient and a homozygous mutation (c. 814_815insG) in another patient, all three variants are novel. Further analysis of the splicing pattern in a minigene construct showed that the c. 1439+1G>C mutation can lead to the retainment of intron 9 as the 5'-donor splice site disappears during post-transcriptional processing of mRNA. In conclusion, our study identified three novel SCNN1A gene mutations in two Chinese patients with systemic PHA1.