title: Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21.
abstract: Essential hypertension is a common multifactorial trait. The molecular basis of a number of rare diseases that after blood pressure in humans has been established, identifying pathways that may be involved in more common forms of hypertension. Pseudohypoaldosteronism type II (PHAII, also known as familial hyperkalaemia and hypertension or Gordon's syndrome; OMIM #145260), is characterized by hyperkalaemia despite normal renal glomerular filtration, hypertension and correction of physiologic abnormalities by thiazide diuretics. Mild hyperchloremia, metabolic acidosis and suppressed plasma renin activity are variable associated findings. The pathogenesis of PHAII is unknown, although clinical studies indicate an abnormality in renal ion transport. As thiazide diuretics are among the most efficacious agents in the treatment of essential hypertension, understanding the pathogenesis of PHAII may be of relevance to more common forms of hypertension. Analysis of linkage in eight PHAII families showing autosomal dominant transmission demonstrates locus heterogeneity of this trait, with a multilocus lod score of 8.1 for linkage of PHAII to chromosomes 1q31-q42 and 17p11-q21. Interestingly, the chromosome-17 locus overlaps a syntenic interval in rat that contains a blood pressure quantitative trait locus (QTL). Our findings provide a first step toward identification of the molecular basis of PHAII.
authors.affiliation: Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Mansfield
authors.forename: D B
authors.initials: DB
authors.lastname: Simon
authors.forename: Z
authors.initials: Z
authors.lastname: Farfel
authors.forename: M
authors.initials: M
authors.lastname: Bia
authors.forename: J R
authors.initials: JR
authors.lastname: Tucci
authors.forename: M
authors.initials: M
authors.lastname: Lebel
authors.forename: M
authors.initials: M
authors.lastname: Gutkin
authors.forename: B
authors.initials: B
authors.lastname: Vialettes
authors.forename: M A
authors.initials: MA
authors.lastname: Christofilis
authors.forename: R
authors.initials: R
authors.lastname: Kauppinen-Makelin
authors.forename: H
authors.initials: H
authors.lastname: Mayan
authors.forename: N
authors.initials: N
authors.lastname: Risch
authors.forename: R P
authors.initials: RP
authors.lastname: Lifton
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006947:Hyperkalemia / Q000150:complications / Q000235:genetics*; D006973:Hypertension / Q000150:complications / Q000235:genetics*; D008297:Male; D010375:Pedigree; D011546:Pseudohypoaldosteronism / Q000150:complications / Q000235:genetics*; D051381:Rats