Abstract
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.
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Acknowledgements
We thank the family for their enthusiastic cooperation and hospitality, Mrs Ingrid Laurendeau, Drs Guy Lalau and Pierre-Oliver Schischmanoff for performing some of the preliminary parts of the investigation, and Pr Gil Tchernia for stimulating discussions. We thank Margaret Chetty for excellent technical assistance. This work was supported by Telethon (prog. E0783, prog. GP0202Y02), by AIRC, Associazione per la Lotta al Neuroblastoma, Progetto ACRO-CNR and MURST progetti PRIN (Italy) and by MIUR FIRB project (AI), the INSERM (U 473) and the INSERM/AFM (Project no 4MR09F) (JD), and the Sir Jules Thorn Trust for funding (GWS).
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Carella, M., d'Adamo, A., Grootenboer-Mignot, S. et al. A second locus mapping to 2q35–36 for familial pseudohyperkalaemia. Eur J Hum Genet 12, 1073–1076 (2004). https://doi.org/10.1038/sj.ejhg.5201280
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DOI: https://doi.org/10.1038/sj.ejhg.5201280
