Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity

Albertina So, David L. Duffy, Richard D. Gordon, Yvette W.A. Jeske, Karen Lin-Su, Maria I. New, Michael Stowasser

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Background: Familial hyperaldosteronism type II (FH-II) is characterized by the familial occurrence of primary aldosteronism; unlike FH-I, it is not glucocorticoid-remediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. Linkage to a 5-Mbp region of chromosome 7p22 was previously reported in an Australian family with eight affected members. Mutations in the exons or intron-exon boundaries of PRKAR1B (7p22, closely related to PRKAR1A, which is mutated in Carney complex) have been excluded in this family. Objective: To refine the region of linkage, and to seek evidence of linkage in a South American family and in three other Australian families with FH-II, using seven closely spaced markers at 7p22. Methods: To establish phenotypes (affected, uncertain or unaffected), blood pressure, plasma aldosterone and plasma renin (activity or concentration) were measured and the aldosterone: renin ratio (ARR) calculated. Individuals with consistently increased ARR underwent fludrocortisone suppression testing. The genotypes of the five pedigrees were analysed using seven closely spaced microsatellite markers at 7p22, and two-point and multipoint logarithm of odds (LOD) scores were calculated to assess linkage with FH-II. Results: The combined multipoint LOD score for three families (the original Australian, the South American and a new Australian family) showing linkage at 7p22 was highly significant at 4.61 (θ = 0) for markers D7S462 and D7S517. A newly found recombination event in the first Australian family narrowed the area of linkage by 1.8 Mbp, permitting exclusion of approximately half the candidate genes in the originally reported locus. It was not possible to demonstrate linkage at the 7p22 region in the remaining two Australian families. Conclusion: This study provides further evidence for linkage of FH-II to 7p22, refines the locus, and supports the notion that FH-II may be genetically heterogeneous.

Original languageEnglish
Pages (from-to)1477-1484
Number of pages8
JournalJournal of Hypertension
Volume23
Issue number8
DOIs
StatePublished - Aug 2005

Keywords

  • Familial
  • Genetic
  • Hypertension
  • Linkage
  • Primary aldosteronism

Fingerprint

Dive into the research topics of 'Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity'. Together they form a unique fingerprint.

Cite this