Further study of chromosome 7p22 to identify the molecular basis of familial hyperaldosteronism type II

• Published in: Journal of human hypertension Vol. 25; no. 9; pp. 560 - 564
• Main Authors: Carss, K J, Stowasser, M, Gordon, R D, O'Shaughnessy, K M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2011; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/208/737; 692/699/2743/1279; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Chromosome 7; Chromosomes; Chromosomes, Human, Pair 7; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Copy number; Endocrine disorders; Epidemiology; Forkhead Transcription Factors - genetics; Genetic aspects; Genotype; Health Administration; Humans; Hyperaldosteronism; Hyperaldosteronism - genetics; Hypertension; Karyotypes; Linkage analysis; Medical sciences; Medicine; Medicine & Public Health; Mutation; original-article; Pedigree; Physiological aspects; Polymorphism, Single Nucleotide; Public Health; Single-nucleotide polymorphism; sporadic primary aldosteronism; familial hyperaldosteronism type II; 7p22; virtual karyotype; sequencing; Endocrinopathy; Hypertension; Adrenal cortex diseases; Hyperaldosteronism; Nucleotide sequence; Chromosome; Cardiovascular disease; Hyperadrenocorticism; Adrenal gland diseases
• ISSN: 0950-9240; 1476-5527
• DOI: 10.1038/jhh.2010.93

Familial hyperaldosteronism type II (FH-II) is an inherited form of hyperaldosteronism associated with hypertension in most patients. The mutations that cause FH-II are unknown, but linkage analysis has mapped them to chromosome 7p22. As FH-II is clinically indistinguishable from sporadic primary aldosteronism, a common and treatable condition, unravelling the cause of FH-II has important implications for these sporadic cases. To investigate whether FH-II is caused by large deletions or insertions, we examined the virtual karyotype of four pairs of affected and unaffected individuals using high-density bead chips. We also sequenced the coding regions of five 7p22 candidate genes that were prioritized because of their putative role in cell growth. We found no evidence of single-nucleotide polymorphism (SNP) copy number variation between pairs, and from the widest gap on the chip, chromosome 7p22 deletions or insertions exceeding ∼50 kb in these pedigrees can be excluded. We found 15 SNPs (two of which were novel), but none of them were non-synonymous and segregated with the disease in the FH-II pedigrees. We have been able to exclude large genomic deletions or insertions at 7p22 and refine the candidate gene list for this locus, but the mutations causing FH-II remain elusive.