title: Two novel mutations of the CYP11B2 gene in a Japanese patient with aldosterone deficiency type 1.
abstract: Isolated hypoaldosteronism is a rare and occasionally life-threatening cause of salt wasting in infancy.  A 2-month-old Japanese boy of unrelated parents was examined for failure to thrive and poor weight gain.  Laboratory findings were hyponatremia, hyperkalemia, high plasma renin and low aldosterone levels.  Spot urine analysis by gas chromatography-mass spectrometry (GC-MS) showed that urinary excretion of corticosterone metabolites was elevated.  Whereas excretion of 18-hydroxycortricosterone metabolites was within the normal range, excretion of aldosterone metabolites was undetectable.  The patient was therefore suspected to have aldosterone synthase deficiency type 1.  Sequence analysis of CYP11B2, the gene encoding aldosterone synthase (CYP11B2), showed that the patient was a compound heterozygote for c.168G>A, p.W56X in exon 1 and c.1149C>T, p.R384X in exon 7.  p.W56X was inherited from his mother and p.R384X was from his father.  Since both alleles contain nonsense mutations, a lack of CYP11B2 activity was speculated to cause his condition.  To our knowledge, this is the first Japanese patient in which the molecular basis of aldosterone synthase deficiency type 1 has been clarified.  This case also indicates that spot urinary steroid analysis is useful for diagnosis.
authors.affiliation: Department of Pediatrics, Obihiro Kyoukai Hospital, Obihiro 080-0805, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Kondo
authors.forename: Akie
authors.initials: A
authors.lastname: Nakamura
authors.forename: Keiko
authors.initials: K
authors.lastname: Homma
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Narugami
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hattori
authors.forename: Hayato
authors.initials: H
authors.lastname: Aoyagi
authors.forename: Katsura
authors.initials: K
authors.lastname: Ishizu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tajima
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D006994:Hypoaldosteronism / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation
chemical_list: D019405:Cytochrome P-450 CYP11B2