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 differ ent 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. Design and methods Clinical, biological and genetic analyses were made of t hree kindreds, including 11 affected individuals among 25 members. Genotypi ng was performed using four series of microsatellite markers spanning the c hromosomes 1, 17 and 12 loci, and the thiazide-sensitive Na-Cl cotransporte r (SLC12A3) gene. Results Segregation of the trait in each kindred was compatible with an aut osomal transmission, the affected individuals displaying reasonably consist ent biochemical abnormalities and the expected variability in arterial hype rtension. Multipoint linkage analysis excluded linkage with the four candid ate loci in kindreds 1 and 2, but not with the chromosome 1 locus in kindre d 3. Conclusion These results demonstrate further genetic heterogeneity and that a fourth gene is responsible for FHH in at least two unrelated kindreds. T hey suggest a variety of molecular defects leading to FHH. (C) 2001 Lippinc ott Williams & Wilkins.