Abstract
Finding genes that cause human hypertension is not straightforward, since the determinants of blood pressure in primary hypertension are multifactorial1. One approach to identifying relevant genes is to elucidate rare forms of monogenic hypertension. A relevant mutation may provide a rational starting point from which to analyse the pathophysiology of a condition affecting 20% of the world's population. In 1973 a family with autosomal dominantly inherited brachydactyly and severe hypertension, where the two traits cosegregated completely, was described2. We have now re-examined this kindred, and localized the hypertension and brachydactyly locus to chromosome 12p in a region defined by markers D12S364 and D12S87. As the renin-angiotensin-system and sympathetic nervous system respond normally in this form of hypertension, the condition resembles essential hypertension. This feature distinguishes this form of hypertension from glucocorticoid remediable aldosteronism and Liddle,s syndrome, which are salt-sensitive forms of monogenic hypertension with very low plasma renin activity3–7. We suggest that identification of the gene involved in hypertension and brachydactyly and its mutation will be of great relevance in elucidating new mechanisms leading to blood pressure elevation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lifton, R.R. & Jeunemaitre, X. Finding genes that cause human hypertension. J. Hypertens. 11, 231–236 (1993).
Bilginturan, N., Zileli, S., Karacadag, S. & Pirnar, T. Hereditary brachydactyly associated with hypertension. J. Med. Genet. 10, 253–259 (1973).
Ulick, S. et al. Defective fasciculata zone function as the mechanism of glucocorticoid-remediable aldosteronism. J. Clin. Endocrinol. Metab. 71, 1151–1157 (1990).
Rich, G.M. et al. Glucocorticoid-remediable aldosteronism in a large kindred: clinical spectrum and diagnosis using a characteristic biochemical phenotype. Ann. Intern. Med. 116, 813–820 (1992).
Lifton, R.P. et al. A chimaeric 11 β-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. 355, 262–265 (1992).
Shimkets, R.A. et al. Liddle,s syndrome: Heritable human hypertension caused by mutations in the B subunit of the epithelial sodium channel. Cell 79, 407–414 (1994).
Hansson, J.H. et al. Hypertension caused by a truncated epithelial sodium channel γ subunit: genetic heterogeneity of Liddle syndrom. Nature Genet. 11, 76–82 (1995).
Spiegel, A.M., Pseudohypoparathyroidism in The Metabolic Basis Of Inherited Disease. (eds Scriver, C.R., Beaudet, A.L., Sly, W.S. & Valle, D.) 2013–2027 (McGraw-Hill, New York, 1989).
Wilson, L.C. et al. Brachydactyly and mental retardation: an Albright hereditary osteodystrophy-like syndrome localized to 2q37. Am. J. Hum. Genet. 56, 400–407 (1995).
Haller, H., Lindschau, C., Quass, P., Distler, A. & Luft F.C. Differentiation of vascular smooth muscle cells and the regulation of protein kinase C-α. Circ.Res. 76, 21–29 (1995).
Takahashi, K. et al. Parathyroid hormone-related peptide as a locally produced vasorelaxant: regulation of its mRNA by hypertension in rats. Biochem. Biophys. Res. Comm. 208, 447–455 (1995).
Karaplis, A.C. et al. Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev. 8, 277–289 (1994).
Gyapay, G. et al. Genethon human genetic linkage map. Nature Genet. 7, 246–339 (1994).
Ziegle, J. Application of automated DNA sizing technology for genotyping microsatellite loci. Genomics. 14, 1026–1031 (1992).
Weeks, D.E., Ott, J. & Lathrop, G.M. A general simulation program for linkage analysis. Am. J. Hum. Genet. 47, A204 (abstr.) (1990).
Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans. Proc. Natl. Acad. Sci. USA 81, 3443–3446 (1984).
Cottingham, R.W. Jr., Idury, R.M. & Schäffer, A.A. Faster sequential genetic linkage computations. Am. J. Hum. Genet. 53, 252–263 (1993).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schuster, H., Wienker, T., Bähring, S. et al. Severe autosomal dominant hypertension and brachydactyly in a unique Turkish kindred maps to human chromosome 12. Nat Genet 13, 98–100 (1996). https://doi.org/10.1038/ng0596-98
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0596-98
This article is cited by
-
Molekulargenetik der humanen Hypertonie
Der Internist (2021)
-
Whole-exome sequencing identifies a de novo PDE3A variant causing autosomal dominant hypertension with brachydactyly type E syndrome: a case report
BMC Medical Genetics (2020)
-
A PDE3A mutation in familial hypertension and brachydactyly syndrome
Journal of Human Genetics (2016)
-
New Developments in the Genetics of Hypertension: What Should Clinicians Know?
Current Cardiology Reports (2015)
-
PDE3A mutations cause autosomal dominant hypertension with brachydactyly
Nature Genetics (2015)