Novel mutation in the SLC12A3 gene in a Sri Lankan family with Gitelman syndrome & coexistent diabetes: a case report.
Novel mutation in the SLC12A3 gene in a Sri Lankan family with Gitelman syndrome & coexistent diabetes: a case report.
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DOI：
10.1186/s12882-017-0563-0
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发表时间：
2017-04-26
期刊：
影响因子：
2.3
通讯作者：
Dissanayake VHW
中科院分区：
文献类型：
--
作者：
Subasinghe CJ;Sirisena ND;Herath C;Berge KE;Leren TP;Bulugahapitiya U;Dissanayake VHW
Gitelman综合征（GS）是一种罕见的常染色体Recombinant遗传性盐耗性肾小管病，与SLC 12 A3基因突变相关，该基因编码肾脏中的NaCl协同转运蛋白（NCC）。在这份报告中，我们描述了两个兄弟姐妹从斯里兰卡非血缘家庭提出与肾性钾消耗，低镁血症，低钙尿症和高肾素性高醛固酮血症与正常血压相关的低钾血症。遗传检测显示，两人均为SLC 12 A3基因外显子10中新型错义突变的纯合子[NM_000339. 2，c.1276A > T; p.N426Y]，该突变先前未在与GS相关的文献中报道。他们的母亲是同一突变的杂合子携带者。父亲在检查时已不在人世。这种新的突变扩展了已知SLC 12 A3基因突变的范围，并进一步支持GS的等位基因异质性。有趣的是，两个兄弟姐妹都有年轻发病的糖尿病，有很强的家族史。这些研究结果在提供适当的遗传咨询，以家庭方面的风险与近亲繁殖，检测携带者/前驱亲属的影响。它进一步扩展了已知的Gitelman综合征的基因型和表型特征谱。
Gitelman syndrome (GS) is a rare autosomal recessively inherited salt-wasting tubulopathy associated with mutations in the SLC12A3 gene, which encodes for NaCl cotransporter (NCC) in the kidney. In this report, we describe two siblings from a Sri Lankan non-consanguineous family presenting with hypokalaemia associated with renal potassium wasting, hypomagnesemia, hypocalciuria and hypereninemic hyperaldosteronism with normal blood pressure. Genetic testing showed that both were homozygotes for a novel missense mutation in exon 10 of the SLC12A3 gene [NM_000339.2, c.1276A > T; p.N426Y], which has not previously been reported in the literature in association with GS. Their mother was a heterozygous carrier for the same mutation. The father was not alive at the time of testing. This novel mutation extends the spectrum of known SLC12A3 gene mutations and further supports the allelic heterogeneity of GS. Interestingly both siblings had young onset Diabetes with strong family history. These findings have implications in providing appropriate genetic counseling to the family with regard to the risk associated with inbreeding, the detection of carrier/presymptomatic relatives. It further expands the known spectrum of genotypic and phenotypic characteristics of Gitelman syndrome.