Luft FC, Bahring S, Schuster H, Wiendker T, Toka H, Toka O,
Naraghi R, Haller H
Construction of a physical map and additional phenotyping in
autosomal dominant hypertension and brachydactyly, which maps
to chromosome 12
Am Soc Nephrol
J Am Soc Nephrol (abstract)
(Sep) 7:1553 1996
Autosomal-dominant hypertension with brachydactyly is a rare cause of
hypertension. Affected persons die of stroke before the age of 50
years, with normal function of the renin-angiotensin and sympathetic
nervous system in response to volume expansion and contraction.
Therefore, this rare disorder shares some features of essential
hypertension. Since patients with this condition are likely to have a
single genetic defect (as apposed to a multifactorial cause of
essential hypertension), this is an attractive population to study.
The authors found an additional similarity: All 7 patients (and none
of 6 controls) had loops in the posterior inferior cerebellar artery,
which may impinge on the ventrolateral medulla and elicit a
neurogenic form of hypertension. Similar loops are found in essential
hypertension. The disorder has been mapped to chromosome 12p, and a
family in Japan as a 3-megabase deletion in that region. This narrows
the focus genes in the vicinity. So far, they have excluded genes for
the L-type calcium channel and PTH receptor.
Comment: This abstract uses positional cloning to find the gene
responsible for the defect using family studies, without any
knowledge of the basis of the genetic defect. For example, the PCKD
gene was discovered by positional cloning. This type of cloning will
be greatly aided by the Human Genome Project, because 1) localization
of the genetic defect will be aided by the large number of PCR markers
spanning the genome, 2) candidate genes will be obvious by position on
the genome, and 3) yeast artificial chromosomes will be available for
all regions of the chromosome. (Robert A. Star, M.D.,
University of Texas Southwestern Medical School, Dallas)
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Am Soc Nephrol
H: Pathophysiology :
Genetics
H: Pathophysiology :
Stroke