Genetic heterogeneity of familial hyperkalaemic hypertension.
BACKGROUND
Familial hyperkalaemic hypertension (FHH) is a Mendelian form of low-renin hypertension characterized by hyperkalaemia and hyperchloraemic acidosis despite a normal glomerular filtration rate. To date, three different loci have been identified, on chromosomes 1, 17 and 12.


OBJECTIVE
To test for genetic linkage between the three FHH loci and three new affected kindreds.


METHODS
Clinical, biological and genetic analyses were made of three kindreds, including 11 affected individuals among 25 members. Genotyping was performed using four series of microsatellite markers spanning the chromosomes 1, 17 and 12 loci, and the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene.


RESULTS
Segregation of the trait in each kindred was compatible with an autosomal transmission, the affected individuals displaying reasonably consistent biochemical abnormalities and the expected variability in arterial hypertension. Multipoint linkage analysis excluded linkage with the four candidate loci in kindreds 1 and 2, but not with the chromosome 1 locus in kindred 3.


CONCLUSIONS
These results demonstrate further genetic heterogeneity and that a fourth gene is responsible for FHH in at least two unrelated kindreds. They suggest a variety of molecular defects leading to FHH.
Disse-Nicodeme
S
S
INSERM U36, Collège de France, Paris.
Desitter
I
I
Fiquet-Kempf
B
B
Houot
A M
AM
Stern
N
N
Delahousse
M
M
Potier
J
J
Ader
J L
JL
Jeunemaitre
X
X
D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006947:Hyperkalemia / Q000150:complications*; D006973:Hypertension / Q000209:etiology* / Q000235:genetics*; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011546:Pseudohypoaldosteronism / Q000145:classification / Q000235:genetics; D011955:Receptors, Drug; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
D002352:Carrier Proteins; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor