A second locus mapping to 2q35–36 for familial pseudohyperkalaemia

• Published in: European journal of human genetics : EJHG Vol. 12; no. 12; pp. 1073 - 1076
• Main Authors: Carella, Massimo, d'Adamo, Adamo Pio, Grootenboer-Mignot, Sabine, Vantyghem, Marie C, Esposito, Laura, D'Eustacchio, Angela, Ficarella, Romina, Stewart, Gordon W, Gasparini, Paolo, Delaunay, Jean, Iolascon, Achille
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2004; Nature Publishing; Nature Publishing Group
• Subjects: Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cations; Chromosome 16; Chromosome 2; Chromosome Mapping; Chromosomes, Human, Pair 2; Cytogenetics; Errors of metabolism; Erythrocytes - metabolism; Female; Gene Expression; Gene mapping; Genes; Genetics; Haplotypes; Hematologic Diseases - genetics; Hematologic Diseases - metabolism; Human Genetics; Humans; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mutation; Pedigree; Potassium; Potassium - metabolism; Proteins; short-report; Software; Temperature effects; France; Italy; Edinburgh Scotland; pseudohyperkalaemia; erythrocytes; 2q35–36; Genetic mapping; Hyperkaliemia; Metabolic disorder; Hydroelectrolytic balance disorder; Family study; Chromosome A2; Genetics; Pseudohyperkalaemia; Inorganic element
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/sj.ejhg.5201280

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.