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Abstract:
Am Soc Nephrol Ann Mtg -- Miami
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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
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