title: Clinical and molecular analysis of six Japanese patients with a renal form of pseudohypoaldosteronism type 1.
abstract: Pseudohypoaldosteronism type 1 (PHA1) is a rare condition characterized by neonatal salt loss with elevated plasma aldosterone and renin levels. Two types of PHA1 have been described: an autosomal recessive systemic form and an autosomal dominant renal form, in which the target organ defect is confined to the renal tubules. The dominant renal form of PHA1 is caused by heterozygous mutations in the NR3C2 gene, which encodes the mineralocorticoid receptor (MR). We determined clinical and biochemical parameters in two familial and four sporadic Japanese patient and analyzed the status of the NR3C2 gene. Failure to thrive was noted in five of the six patients. In one of the familial cases, the mother had an episode of failure to thrive when she was a toddler, but received no medical treatment. NaCl supplementation was discontinued in four of the six patients after they reached one year of age and they have grown normally thereafter. However, in one patient, 9 g/day of salt has been required to maintain serum Na concentration after 1 year of age. Analysis of NR3C2 identified three novel mutations [c. C1951T (p.R651X), c.304_305delGC (p.A102fsX103), c.del 603A (p.T201fsX34)] and one previously reported mutation [c.A2839G (p.947X)]. p.R651X was identified in one familial case and one unrelated sporadic patient. The patient who has been supplemented with large amount of salt was heterozygous for c.del 603A in exon 2. In conclusion, our study expands the spectrum of phenotypes, and characterized mutations of NR3C2 in the renal form of PHA1.
authors.affiliation: Department of Pediatrics, Tosei General Hospital, Seto 489-0065, Japan.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Hatta
authors.forename: Akie
authors.initials: A
authors.lastname: Nakamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Hara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamijo
authors.forename: Junko
authors.initials: J
authors.lastname: Iwata
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamajima
authors.forename: Marie
authors.initials: M
authors.lastname: Abe
authors.forename: Mari
authors.initials: M
authors.lastname: Okada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ushio
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Tsuyuki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
mesh_terms: D000450:Aldosterone / Q000097:blood; D005183:Failure to Thrive / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D007684:Kidney Tubules / Q000503:physiopathology*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011546:Pseudohypoaldosteronism / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: C561839:NR3C2 protein, human; D018161:Receptors, Mineralocorticoid; D012965:Sodium Chloride; D000450:Aldosterone; D012083:Renin