Genomic structure of the human gene for protein kinase A regulatory subunit R1-beta (PRKAR1B) on 7p22: No evidence for mutations in familial hyperaldosteronism type II in a large affected kindred

Elphinstone, Martin S., Gordon, Richard D., So, Albertina, Jeske, Yvette W. A., Stratakis, Constantine A. and Stowasser, Michael (2004) Genomic structure of the human gene for protein kinase A regulatory subunit R1-beta (PRKAR1B) on 7p22: No evidence for mutations in familial hyperaldosteronism type II in a large affected kindred. Clinical Endocrinology, 61 6: 716-723. doi:10.1111/j.1365-2265.2004.02155.x


Author Elphinstone, Martin S.
Gordon, Richard D.
So, Albertina
Jeske, Yvette W. A.
Stratakis, Constantine A.
Stowasser, Michael
Title Genomic structure of the human gene for protein kinase A regulatory subunit R1-beta (PRKAR1B) on 7p22: No evidence for mutations in familial hyperaldosteronism type II in a large affected kindred
Journal name Clinical Endocrinology   Check publisher's open access policy
ISSN 0300-0664
1365-2265
Publication date 2004-12
Sub-type Article (original research)
DOI 10.1111/j.1365-2265.2004.02155.x
Volume 61
Issue 6
Start page 716
End page 723
Total pages 8
Place of publication Oxford, U.K.
Publisher Blackwell Scientific Publications
Language eng
Subject 11 Medical and Health Sciences
1115 Pharmacology and Pharmaceutical Sciences
1116 Medical Physiology
1103 Clinical Sciences
110306 Endocrinology
Formatted abstract
Objective:  Familial hyperaldosteronism type II (FH-II) is characterized by inheritance of primary aldosteronism (PAL) but, unlike FH-I, is not glucocorticoid remediable and not associated with the hybrid CYP11B1/CYP11B2 gene mutation. Analysis of two pedigrees previously demonstrated linkage of FH-II with a locus at chromosome 7p22. We sought to determine whether mutations in the exons or intron/exon boundaries in PRKAR1B (encoding protein kinase A regulatory subunit R1-beta), which resides within the linked locus, are associated with FH-II.

Methods: 
Primers enabling sequencing of all exons and intron/exon boundaries were designed by BLAT search using known mRNA sequence, and comparison with an orthologous mouse gene. Sequences from four affected and two unaffected subjects from an Australian family with FH-II demonstrating linkage at 7p22 were compared with published sequences.

Results:  A probable two-nucleotide GenBank sequence error, resulting in an amino acid change, was detected. Two of seven single nucleotide polymorphisms (SNPs) identified were in exons and five in introns. Neither exon-localized SNP resulted in an amino acid change. All intron-localized SNPs were at least 16 nucleotides from the closest intron/exon boundary and therefore unlikely to interfere with gene splicing. Importantly, none of the identified SNPs was exclusively associated with affectation status.

Conclusions: 
Mutations in the exons or intron/exon boundaries of PRKAR1B do not appear to be responsible for FH-II in this family, but a mutation in the promoter or remaining intronic or 5' or 3' untranslated regions could be. Alternatively, a mutation within another gene residing at the 7p22 locus may be responsible.
Keyword Hyperaldosteronism type II
FH-II
Chromosome 7p22
Protein kinase A
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Created: Mon, 13 Aug 2007, 15:21:28 EST