Vargas-Poussou R.,Assistance Publique Hopitaux de Paris |
Vargas-Poussou R.,French Institute of Health and Medical Research |
Vargas-Poussou R.,University of Paris Descartes |
Dahan K.,Catholic University of Louvain |
And 27 more authors.
Journal of the American Society of Nephrology | Year: 2011
Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene. Copyright © 2011 by the American Society of Nephrology.
Otto M.-P.,Laboratoire Of Biologie |
Cheminel V.,Laboratoire Of Biochimie |
Crevon L.,Service de medecine interne |
Dubourg L.,Service dexploration fonctionnelle renale et metabolique |
And 3 more authors.
Annales de Biologie Clinique | Year: 2011
We report the case of an asymptomatic patient presenting a severe chronic renal hypokalaemia. Once being sure of no diuretics use, two hypothesis can be mentioned for a normotensive patient presenting an hypokalaemia associated with a metabolic alcalosis: Bartter syndrome or Gitelman syndrome. The highlighting of low magnesaemia and hypocalciuria strongly concentrates the diagnosis on Gitelman syndrome. First, this has been strengthened by the results of renal fonction tests and later it has confirmed by molecular diagnosis with the identification of a known homozygous mutation on SLC12A3 gene. In the patient family, the same chromosomal abnormality has been found in the young sister. For these two patients the treatment ordered is an antikaliuretic diuretic, magnesium and potassium supplements. This case shows the difficulty to diagnose Gitelman syndrome: it is frequently mistaken for Bartter syndrome. The main differences between these two syndromes are magnesaemia and calciuria. Furthemore, patients with Gitelman syndrome are often asymptomatic, this explains why prevalence of this illness is probably underestimated.
Dubourg L.,Service dExploration Fonctionnelle Renale et Metabolique |
Dubourg L.,University of Lyon |
Dubourg L.,French Institute of Health and Medical Research |
Hadj-Aissa A.,Service dExploration Fonctionnelle Renale et Metabolique |
And 4 more authors.
Analytical Biochemistry | Year: 2010
Inulin or polyfructosan clearance is regarded as the most accurate method of assessing the glomerular filtration rate. We propose an enzymatic method of polyfructosan determination based on the hydrolysis of polyfructosan into fructose by inulinase and the elimination of the interfering quantity of glucose by glucose oxidase. This spectrophotometric microplate formatted assay, which demonstrated very good specificity and reproducibility (within-run precision <1% and between-run precision <3.5%), is cheap and simple to perform and can be used by all analytical laboratories and in all clinical conditions. © 2010 Elsevier Inc.