title: Congenital hyperreninemic hypoaldosteronism in Israel: sequence analysis of CYP11B2 gene.
abstract: OBJECTIVE
  Isolated aldosterone biosynthesis defect causing congenital hyperreninemic hypoaldosteronism with otherwise normal adrenal function usually results from aldosterone synthase deficiency. Patients present with manifestations of mineralocorticoid deficiency during the first weeks of life. The largest numbers of cases have been described in Iranian Jews, who carried concomitantly two homozygous missense mutations (R181W and V386A). In a few cases with presumed aldosterone synthase deficiency no mutations in CYP11B2 gene have been identified. We describe a molecular and endocrine evaluation of seven cases of congenital hyperreninemic hypoaldosteronism in Israel.
  
  
  METHODS
  Two of the six Jewish patients are of Iranian origin. The parents of five other patients originated from Yemen, Syria and Morocco. One patient is a Muslim-Arab. CYP11B2's exons, exon-intron boundaries and promoter region were sequenced by multiple PCR amplifications. Gene size determination was performed either by long-range PCR or by Southern blot analysis.
  
  
  RESULTS
  Only two patients (Iranian Jews) carried a known homozygous R181W, V386A mutations, other two were compound heterozygotes for either the R181W or V386A and one additional novel amino acid substitution (A319V or D335G), and one patient was found to be a carrier of the two novel variations (A319V and D335G). We could not find a molecular defect in 2 patients: one was a carrier of the D335G mutation and the other had no detectable molecular change in the coding and promoter regions.
  
  
  CONCLUSIONS
  The genetic and molecular basis of congenital hyperreninemic hypoaldosteronism is more heterogeneous than previously described. The significance of amino acid substitutions identified in this study remains to be determined.
authors.affiliation: Molecular Genetics Laboratory, E. Wolfson Medical Center, Holon, Israel. leshinsky@wolfson.health.gov.il
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
authors.forename: Zohar
authors.initials: Z
authors.lastname: Landau
authors.forename: Sema
authors.initials: S
authors.lastname: Unlubay
authors.forename: Tzvy
authors.initials: T
authors.lastname: Bistrizer
authors.forename: Amnon
authors.initials: A
authors.lastname: Zung
authors.forename: Yardena
authors.initials: Y
authors.lastname: Tenenbaum-Rakover
authors.forename: Liat
authors.initials: L
authors.lastname: Devries
authors.forename: Dorit
authors.initials: D
authors.lastname: Lev
authors.forename: Aaron
authors.initials: A
authors.lastname: Hanukoglu
mesh_terms: D003299:Cooperative Behavior; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D006801:Humans; D006994:Hypoaldosteronism / Q000097:blood / Q000151:congenital* / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D007557:Israel; D008297:Male; D017422:Sequence Analysis, DNA
chemical_list: D019405:Cytochrome P-450 CYP11B2