A familial case of pseudohypoaldosteronism type II (PHA2) with a novel mutation (D564N) in the acidic motif in WNK4.
A familial case of pseudohypoaldosteronism type II (PHA2) with a novel mutation (D564N) in the acidic motif in WNK4.
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II 型假性醛固酮增多症 (PHA2) 家族病例，WNK4 酸性基序出现新突变 (D564N)。
DOI：
10.1002/mgg3.705
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Takaichi K.
中科院分区：
文献类型：
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作者：
Sakoh T;Sekine A;Mori T;Mizuno H;Kawada M;Hiramatsu R;Hasegawa E;Hayami N;Yamanouchi M;Suwabe T;Sawa N;Ubara Y;Fujimaru T;Sohara E;Shinichi U;Hoshino J;Takaichi K.
背景至今仍有少数病例报告的假性醛固酮减少症II型（PHA 2），也被称为戈登综合征，基因诊断，这是第一个报告的家族性PHA 2的情况下，在日本与一个新的D564 N突变在WNK 4。方法一个29岁的女性，因为高钾血症（血清钾：6.4 mmol/L）被收住我院。她有轻度高血压（135/91 mm Hg），碳酸氢盐水平处于正常范围下限（HCO 3：22 mmol/L），阴离子间隙正常，血浆肾素活性低（0.2 ng ml-1hr-1），尿钙排泄量高（505.4 mg/g Cre）。怀疑是遗传性疾病，因为她的母亲也有同样的症状。我们对主要的遗传性肾脏疾病进行了全面的遗传分析，包括负责PHA 2的基因（WNK 1，WNK 4，KLHL 3和CUL 3）。结果遗传分析显示，患者和她的母亲在WNK 4的酸性基序中有一个新的错义突变（D564 N），导致PHA 2的诊断。三氯噻嗪（1毫克/天）的管理有效地改善了她的血压（114/69毫米汞柱），血浆碳酸氢盐（25 mmol/L），血清钾（4.3 mmol/L），尿钙排泄（27.2毫克/克Cre）。WNK 4基因D564 N突变是PHA 2的一个新的遗传病因，其表型相对较轻。
BackgroundThere have been still few case reports of pseudohypoaldosteronism type II (PHA2), also known as Gordon's syndrome, genetically diagnosed, and this is the first report of familial PHA2 case in Japan with a novel D564N mutation inWNK4.MethodsA 29‐year‐old woman was admitted to our hospital due to hyperkalemia (serum potassium: 6.4 mmol/L). She had mild hypertension (135/91 mm Hg), a bicarbonate level at the lower limit of the normal range (HCO3: 22 mmol/L) with a normal anion gap, low plasma renin activity (0.2 ng ml‐1hr‐1), and high urinary calcium excretion (505.4 mg/g Cre). A hereditary condition was suspected because her mother also had the same symptoms. We performed a comprehensive genetic analysis for major inherited kidney diseases with next‐generation sequencing including the genes responsible for PHA2 (WNK1,WNK4,KLHL3, andCUL3).ResultsGenetic analysis revealed that the patient and her mother had a novel missense mutation (D564N) in the acidic motif inWNK4, which leads to the diagnosis of PHA2. Administration of trichlormethiazide (1 mg/day) effectively ameliorated her blood pressure (114/69 mm Hg), plasma bicarbonate (25 mmol/L), serum potassium (4.3 mmol/L), and urinary calcium excretion (27.2 mg/g Cre).ConclusionWe report the first Japanese familial case of PHA2 withWNK4mutation. D564N mutation inWNK4is a novel genetic cause of PHA2 with a relatively mild phenotype.