Nyström A-M, Bondeson M-L, Skanke N, Mårtensson J, Strömberg B, Gustafsson J, Annerén G
Department of Genetics and Pathology, Uppsala University, S-751 85 Uppsala, Sweden.
J Clin Endocrinol Metab. 2004 Jan;89(1):227-31. doi: 10.1210/jc.2003-030762.
Pseudohypoaldosteronism type I (PHA1) is a condition associated with salt wasting leading to dehydration, hypotension, hyperkalemia, and metabolic acidosis. Sporadic cases and two familial forms, one autosomal dominant and one autosomal recessive form, have been described. The autosomal dominant or sporadic form manifests milder salt wasting that remits with age. Mutations in the gene encoding the mineralocorticoid receptor (MR) have been identified in patients with the autosomal dominant inheritance. However, recent studies suggest that the autosomal dominant and sporadic forms are genetically heterogeneous and that additional genes might be involved. We report on the study of 15 members of a Swedish five-generation family with the autosomal dominant form of PHA1. Interestingly, neuropathy was found in two of five affected individuals. A novel heterozygous nonsense mutation C436X in exon 2 was identified in the index patient by linkage analysis, PCR, and direct sequencing of the MR gene. Analysis of the family demonstrated that the mutation segregated with PHA1 in the family. It is unclear whether the neuropathy is associated with the mutation found. Our results together with previously published data suggest that loss-of-function mutations of the MR gene located at 4q31.1, commonly are associated with the autosomal dominant form of PHA1.
I型假性醛固酮增多症（PHA1）是一种与失盐相关的疾病，可导致脱水、低血压、高钾血症和代谢性酸中毒。已报道过散发病例以及两种家族性形式，一种为常染色体显性遗传，另一种为常染色体隐性遗传。常染色体显性或散发性形式表现为较轻的失盐，随年龄增长可缓解。在常染色体显性遗传患者中已鉴定出编码盐皮质激素受体（MR）的基因突变。然而，最近的研究表明，常染色体显性和散发性形式在遗传上是异质性的，可能涉及其他基因。我们报告了对一个瑞典五代家族中15名患有常染色体显性形式PHA1的成员的研究。有趣的是，在五名受影响个体中的两名发现了神经病变。通过连锁分析、PCR和MR基因直接测序，在索引患者中鉴定出一个位于外显子2的新型杂合性无义突变C436X。对该家族的分析表明，该突变与家族中的PHA1共分离。尚不清楚神经病变是否与所发现的突变有关。我们的结果与先前发表的数据共同表明，位于4q31.1的MR基因功能丧失突变通常与PHA1的常染色体显性形式相关。
