A second locus mapping to 2q35-36 for familial pseudohyperkalaemia.
Familial pseudohyperkalaemia (FP) is a symptomless, dominantly inherited red cell trait, which shows a 'passive leak' of K+ cations into the plasma upon storage of blood at room temperature (or below). There are no haematological abnormalities. The loss of K+ is due to a change in the temperature dependence of the leak. The Scottish case initially described, FP Edinburgh, maps to 16q23-qter. Here we studied a large kindred of Flemish descent with FP, termed FP Lille, which was phenotypically identical to the Edinburgh FP. In FP Lille, however, the responsible locus mapped to 2q35-36, with a Lod score of 8.46 for marker D2S1338. We infer that FP Edinburgh and FP Lille, although they are phenocopies of one another, stem from two distinct loci, FP1 (16q23-qter) and FP2 (2q35-36), respectively. This duality hints at the possibility that the protein mediating the leak might be a heterodimer. No mutation was found in three plausibly candidate genes: the KCNE4 gene, the TUBA1 gene and a predicted gene located in genomic contig NT_005403.
TIGEM, Telethon Institute of Genetics and Medicine, Naples, Italy.
Massimo
M
Carella
Adamo Pio
AP
d'Adamo
Sabine
S
Grootenboer-Mignot
Marie C
MC
Vantyghem
Laura
L
Esposito
Angela
A
D'Eustacchio
Romina
R
Ficarella
Gordon W
GW
Stewart
Paolo
P
Gasparini
Jean
J
Delaunay
Achille
A
Iolascon
D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006239:Haplotypes; D006402:Hematologic Diseases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D010375:Pedigree; D011188:Potassium / Q000378:metabolism*
D011188:Potassium