title: Novel mutations in the SCNN1A gene causing Pseudohypoaldosteronism type 1.
abstract: 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.
authors.affiliation: Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Tingting
authors.initials: T
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Ye
authors.initials: Y
authors.lastname: Shen
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Yu
authors.forename: Yongnian
authors.initials: Y
authors.lastname: Shen
authors.forename: Qihua
authors.initials: Q
authors.lastname: Fu
mesh_terms: D017398:Alternative Splicing; D044466:Asian People; D001483:Base Sequence; D053503:Epithelial Sodium Channels / Q000235:genetics*; D005260:Female; D057809:HEK293 Cells; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011546:Pseudohypoaldosteronism / Q000208:ethnology / Q000235:genetics*; D022821:RNA Splice Sites
chemical_list: D053503:Epithelial Sodium Channels; D022821:RNA Splice Sites; C507045:SCNN1A protein, human