Nathalie Godefroid

Publications (8)35.94 Total impact

• Article: Expanding the clinical spectrum of congenital nephrotic syndrome caused by NPHS1 mutations.

  Nathalie Godefroid, Karin Dahan
  Nephrology Dialysis Transplantation 09/2010; 25(9):2837-9. · 3.40 Impact Factor
• Source

  Available from: Philippe Clapuyt

  Article: Development of renal and iliac aneurysms in a child with generalized infantile myofibromatosis.

  Benoit Brasseur, Christophe F Chantrain, Nathalie Godefroid, Thierry Sluysmans, Christine Anslot, Renaud Menten, Philippe Clapuyt, Sophie Dupont, Christiane Vermylen, Bénédicte Brichard
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  ABSTRACT: Infantile myofibromatosis is a rare disorder characterized by the formation of tumors in the skin, soft tissues, bone, and viscera. We report the case of a 3-week-old girl who presented with severe hypertension due to generalized infantile myofibromatosis including renal involvement. The infant was treated by chemotherapy and showed progressive regression of the tumors. However, her evolution was marked by the development of aneurismal dilations of the renal and iliac arteries as observed in fibromuscular dysplasia. We discuss the possibility of a link between these two mesenchymal disorders.
  Pediatric Nephrology 12/2009; 25(5):983-6. · 2.52 Impact Factor
• Source

  Available from: Benedetta Izzi

  Article: GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets.

  Kathleen Freson, Benedetta Izzi, Veerle Labarque, Monique Van Helvoirt, Chantal Thys, Christine Wittevrongel, Marie Bex, Roger Bouillon, Nathalie Godefroid, Willem Proesmans, Francis de Zegher, Jaak Jaeken, Chris Van Geet
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  ABSTRACT: GNAS is an imprinted region that gives rise to several transcripts, antisense transcripts, and noncoding RNAs, including transcription of RNA encoding the alpha-subunit of the stimulatory G protein (Gsalpha). The complexity of the GNAS cluster results in ubiquitous genomic imprints, tissue-specific Gsalpha expression, and multiple genotype-phenotype relationships. Phenotypes resulting from genetic and epigenetic abnormalities of the GNAS region include Albright's hereditary osteodystrophy, pseudohypoparathyroidism types Ia (PHPIa) and Ib (PHPIb), and pseudopseudohypoparathyroidism (PPHP). The aim was to study the complex GNAS pathology by a functional test as an alternative to the generally used but labor-intensive erythrocyte complementation assay. We report the first platelet-based diagnostic test for Gsalpha hypofunction, supported by clinical, biochemical, and molecular data for six patients with PHPIa or PPHP and nine patients with PHPIb. The platelet test is based on the inhibition of platelet aggregation by cAMP, produced after Gsalpha stimulation. Platelets are easily accessible, and platelet aggregation responses were found to reflect Gsalpha signaling defects in patients, in concordance with the patient's phenotype and genotype. Gsalpha hypofunction in PHPIa and PPHP patients with GNAS mutations was clearly detected by this method. Mildly decreased or normal Gsalpha function was detected in patients with PHPIb with either an overall or exon 1A-only epigenetic defect, respectively. Platelet Gsalpha expression was reduced in both PHPIb patient groups, whereas XLalphas was up-regulated only in PHPIb patients with the broad epigenetic defect. The platelet-based test is a novel tool for establishing the diagnosis of Gsalpha defects, which may otherwise be quite challenging.
  Journal of Clinical Endocrinology &amp Metabolism 10/2008; 93(12):4851-9. · 6.50 Impact Factor
• Article: Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome.

  Eva Riveira-Munoz, Qing Chang, Nathalie Godefroid, Joost G Hoenderop, René J Bindels, Karin Dahan, Olivier Devuyst
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  ABSTRACT: Gitelman syndrome (GS) is a recessive salt-losing tubulopathy that is caused by mutations in the SLC12A3 gene that encodes the sodium-chloride co-transporter (NCC). GS is characterized by significant inter- and intrafamilial phenotype variability, with early onset and/or severe clinical manifestations in some patients. No correlations between the disease variability and the position/nature of SLC12A3 mutations have been investigated thus far. In this study, extensive mutational analyses of SLC12A3 were performed in 27 patients with GS, including genomic DNA sequencing, multiplex ligation-dependent probe amplification, cDNA analysis, and quantification of allele-specific transcripts, in parallel with functional analyses in Xenopus laevis oocytes and detailed phenotyping. Twenty-six SLC12A3 mutations were identified in 25 patients with GS, including eight novel (detection rate 80%). Transcript analysis demonstrated that splicing mutations of SLC12A3 lead to frameshifted mRNA subject to degradation by nonsense-mediated decay. Heterologous expression documented a novel class of NCC mutants with defective intrinsic transport activity. A subgroup of patients presented with early onset, growth retardation, and/or detrimental manifestations, confirming the potential severity of GS. The mutations that were associated with a severe presentation were the combination at least for one allele of a missplicing resulting in a truncated transcript that was downregulated by nonsense-mediated decay or a nonfunctional, cell surface-absent mutant. The most recurrent mutation on the second allele was a newly described NCC mutant that affected the functional properties of the co-transporter. These data suggest that the nature/position of SLC12A3 mutation, combined with male gender, is a determinant factor in the severity of GS and provide new insights in the underlying pathogenic mechanisms of the disease.
  Journal of the American Society of Nephrology 05/2007; 18(4):1271-83. · 9.66 Impact Factor
• Article: A novel splicing mutation in SLC12A3 associated with Gitelman syndrome and idiopathic intracranial hypertension.

  Nathalie Godefroid, Eva Riveira-Munoz, Christine Saint-Martin, Marie-Cécile Nassogne, Karin Dahan, Olivier Devuyst
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  ABSTRACT: We report a case of Gitelman syndrome (GS) in a dizygotic twin who presented at 12 years of age with growth delay, metabolic alkalosis, hypomagnesemia and hypokalemia with inappropriate kaliuresis, and idiopathic intracranial hypertension with bilateral papilledema (pseudotumor cerebri). The patient, her twin sister, and her mother also presented with cerebral cavernous malformations. Based on the early onset and normocalciuria, Bartter syndrome was diagnosed first. However, mutation analysis showed that the proband is a compound heterozygote for 2 mutations in SLC12A3: a substitution of serine by leucine at amino acid position 555 (p.Ser555Leu) and a novel guanine to cytosine transition at the 5' splice site of intron 22 (c.2633+1G>C), providing the molecular diagnosis of GS. These mutations were not detected in 200 normal chromosomes and cosegregated within the family. Analysis of complementary DNA showed that the heterozygous nucleotide change c.2633+1G>C caused the appearance of 2 RNA molecules, 1 normal transcript and 1 skipping the entire exon 22 (r.2521_2634del). Supplementation with potassium and magnesium improved clinical symptoms and resulted in catch-up growth, but vision remained impaired. Three similar associations of Bartter syndrome/GS with pseudotumor cerebri were found in the literature, suggesting that electrolyte abnormalities and secondary aldosteronism may have a role in idiopathic intracranial hypertension. This study provides further evidence for the phenotypical heterogeneity of GS and its association with severe manifestations in children. It also shows the independent segregation of familial cavernomatosis and GS.
  American Journal of Kidney Diseases 11/2006; 48(5):e73-9. · 5.43 Impact Factor
• Article: A new class of mutations involved in Gitelman's syndrome affects the intrinsic activity of the Na-Cl cotransporter NCCT

  Eva Riveira-Munoz, Karin Dahan, Nathalie Godefroid, Qing Chang, Joost G Hoenderop, Rene Bindels, Olivier Devuyst
  Nephrology Dialysis Transplantation 07/2006; 21(4):6. · 3.40 Impact Factor
• Article: Reply to the letter from Holder et al.

  Nathalie Godefroid, Willem Proesmans
  Pediatric Nephrology 12/2003; 19(1):123-123. · 2.52 Impact Factor
• Article: A girl with rickets and nephrocalcinosis.

  Nathalie Godefroid, Willem Proesmans
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  ABSTRACT: A 5-year-old girl presented with short stature. She was found to have rickets due to renal phosphate wasting and nephrocalcinosis. Serum parathyroid hormone was suppressed, 25-OH vitamin D was within the normal range, and 1,25-(OH)(2 )vitamin D was elevated. In addition, she had hypercalciuria, proteinuria, which was partially tubular in origin, and a reduced glomerular filtration rate of 58 ml/min per 1.73 m(2). Treatment with phosphate supplements resulted in healing of the rickets and normalization of the serum 1,25-(OH)(2 )vitamin D level. This patient is an example of hypercalciuric rickets, most likely due to an inherited disorder of phosphate metabolism. Hypercalciuric rickets can be inherited as an autosomal recessive as well as autosomal dominant trait.
  Pediatric Nephrology 07/2003; 18(6):573-5. · 2.52 Impact Factor