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Titolo:
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene
Autore:
Weber, S; Hoffmann, K; Jeck, N; Saar, K; Boeswald, M; Kuwertz-Broeking, E; Meij, IIC; Knoers, NVAM; Cochat, P; Sulakova, T; Bonzel, KE; Soergel, M; Manz, F; Schaerer, K; Seyberth, HW; Reis, A; Konrad, M;
Indirizzi:
Univ Marburg, Dept Pediat, D-35037 Marburg, Germany Univ Marburg MarburgGermany D-35037 pt Pediat, D-35037 Marburg, Germany Max Delbruck Ctr Mol Med, Mikrosatellitenzentrum, Berlin, Germany Max Delbruck Ctr Mol Med Berlin Germany ellitenzentrum, Berlin, Germany Univ Hosp, Dept Pediat, Erlangen, Germany Univ Hosp Erlangen GermanyUniv Hosp, Dept Pediat, Erlangen, Germany Univ Hosp, Dept Pediat, Munster, Germany Univ Hosp Munster GermanyUniv Hosp, Dept Pediat, Munster, Germany Univ Nijmegen Hosp, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands Univ Nijmegen Hosp Nijmegen Netherlands NL-6500 HB Nijmegen, Netherlands Hop Edouard Herriot, Pediat Nephrol Unit, Lyon, France Hop Edouard Herriot Lyon France riot, Pediat Nephrol Unit, Lyon, France Univ Hosp, Dept Pediat, Ostrava, Czech Republic Univ Hosp Ostrava Czech Republic , Dept Pediat, Ostrava, Czech Republic Res Inst Child Nutr, Dortmund, Germany Res Inst Child Nutr Dortmund Germany Inst Child Nutr, Dortmund, Germany Univ Heidelberg, Childrens Hosp, Dept Pediat Nephrol, D-6900 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-6900 ol, D-6900 Heidelberg, Germany Univ Essen Gesamthsch, Childrens Hosp, Dept Pediat Nephrol, Essen, GermanyUniv Essen Gesamthsch Essen Germany Dept Pediat Nephrol, Essen, Germany
Titolo Testata:
EUROPEAN JOURNAL OF HUMAN GENETICS
fascicolo: 6, volume: 8, anno: 2000,
pagine: 414 - 422
SICI:
1018-4813(200006)8:6<414:FHWHAN>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
THICK ASCENDING LIMB; BARTTERS-SYNDROME; RENAL MAGNESIUM; HYPOKALEMIC ALKALOSIS; MG2+; COTRANSPORTER; VARIANT; CHANNEL; KIDNEY; ION;
Keywords:
hypomagnesaemia; hypercalciuria; nephrocalcinosis; renal failure; paracellin-1; PCLN-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Konrad, M Univ Marburg, Dept Pediat, Deutschhausstr 12, D-35037 Marburg, Germany Univ Marburg Deutschhausstr 12 Marburg Germany D-35037 Germany
Citazione:
S. Weber et al., "Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene", EUR J HUM G, 8(6), 2000, pp. 414-422

Abstract

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC, MIM 248250) is a complex renal tubular disorder characterised by hypomagnesaemia, hypercalciuria, advanced nephrocalcinosis, hyposthenuria and progressive renal failure. The mode of inheritance is autosomal recessive. A primary defect in the reabsorption of magnesium in the medullary thick ascendinglimb of the loop of Henle (mTAL) has been proposed to be essential in FHHNC pathophysiology. To identify the underlying genetic defect we performed linkage analysis in eight families, including three with consanguineous marriages. We found linkage to microsatellite markers on chromosome 3q27 with amaximum two-point lod score (Z(max)) of 5.208 for D3S3530 without evidencefor genetic heterogeneity. Haplotype analysis revealed crucial recombination events reducing the critical interval to 6.6 cM. Recently, mutations in the gene PCLN-1, mapping to 3q27 and coding for paracellin-1, were identified by Simon et al (1999) as the underlying genetic defect in FHHNC. Paracellin-1 represents a renal tight junction protein predominantly expressed in the TAL. Mutational analysis in our patient cohort revealed eight differentmutations in the PCLN-1 gene, within six novel mutations. In seven of 13 mutant alleles we detected a Leu151 substitution without evidence for a founder effect. Leu151 is a residue of the first extracellular loop of paracellin-1, the part of the protein expected to bridge the intercellular space and to be important for paracellular conductance. This study confirms the implication of paracellin-1 defects in FHHNC and points to a predominant role of this protein in the paracellular reabsorption of divalent cations in theTAL.

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Documento generato il 14/11/18 alle ore 03:18:57