HDCN Abstract:  Am Soc Nephrol Ann Mtg -- Miami  

Muller D, Hoenderop JG, Meij I, van den Heuvel LA, et al

The human epithelial calcium channel (hECaC): chromosomal mapping and linkage analysis in families with idiopathic hypercalciuria

Am Soc Nephrol Ann Mtg -- Miami
J Am Soc Nephrol (Sep) 10:612A 1999

Recently, we identified ECaC which is expressed in the distal part of the nephron and in the proximal small intestine, where its presence is restricted to the apical membrane (Hoenderop JGJ et al. J. Biol. Chem. 274: 8375-8378, 1999). Functional analysis indicated that ECaC exhibits the expected properties for being the gate-keeper in 1,25-dihydroxyvitamin D3-regulated calcium transport. This channel provides, therefore, an excellent candidate gene for calcium related disorders.

In the present study, the linkage of the human ECaC gene with inherited idiopathic hypercalciuria was investigated.

For the chromosomal localization, an EST was obtained by a BLAST database search based on the known rabbit sequence. Subsequently, a specifically designed primer set was utilized to confirm the homologous human gene locus by using the Stanford G3 Radiation Hybrid Panel™ and the gene mapped to chromosome 7. Based on this result, four flanking microsatellite markers were chosen.

For the linkage analysis, DNA of 50 patients from 8 families with idiopathic hypercalciuria was used. Their clinical appearance varied from the complete absence of symptoms over nephrocalcinosis to severe recurrent calcium-oxalate kidney stones.

Based on a standard calcium loading test, two families with absorptive and 6 families with renal hypercalciuria were identified. Pedigrees of the families implicated the presence of an autosomal dominant mode of inheritance with a high penetrance. Phenotyping was performed by repetitive measurements of calcium excretion (>600 mmol Ca/mmol creatinine) while excluding other underlying diseases.

Haplotype analysis was performed on a semi-automated ABI Prism DNA Sequencer and revealed the absence of linkage to the mapped ECaC gene locus in the tested families.

In conclusion, the gene for ECaC is not involved in the pathogenesis of inherited idiopathic hypercalciuria. However, the performed chromosomal mapping and the selected markers provide the basis for future linkage studies in patients with otherwise unexplained disturbances in calcium metabolism.

Copyright © 1999 American Society of Nephrology