title: Genetic heterogeneity of familial hyperkalaemic hypertension.
abstract: 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.
authors.affiliation: INSERM U36, Collège de France, Paris.
authors.forename: S
authors.initials: S
authors.lastname: Disse-Nicodeme
authors.forename: I
authors.initials: I
authors.lastname: Desitter
authors.forename: B
authors.initials: B
authors.lastname: Fiquet-Kempf
authors.forename: A M
authors.initials: AM
authors.lastname: Houot
authors.forename: N
authors.initials: N
authors.lastname: Stern
authors.forename: M
authors.initials: M
authors.lastname: Delahousse
authors.forename: J
authors.initials: J
authors.lastname: Potier
authors.forename: J L
authors.initials: JL
authors.lastname: Ader
authors.forename: X
authors.initials: X
authors.lastname: Jeunemaitre
mesh_terms: 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
chemical_list: 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