Sandrine Vuillaumier-Barrot

Publications (13)51.72 Total impact

• Article: Expanding the Spectrum of PMM2-CDG Phenotype.

  Sandrine Vuillaumier-Barrot, Bertrand Isidor, Thierry Dupré, Christiane Le Bizec, Albert David, Nathalie Seta
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  ABSTRACT: Congenital Disorders of Glycosylation (CDG) are a group of recently described inborn errors of metabolism affecting glycosylation. CDG are disorders that have been reported with a great variability in the clinical presentation, especially for the most common PMM2-CDG. The classical form is neurologic but severe forms with multisystem disorders and hydrops fetalis have been described. Here, we extend on the opposite end the clinical spectrum to an asymptomatic PMM2-CDG case. The case was the father of a child who died of neonatal galactosemia few days after birth. He presented without any clinical or biological signs, except a typical CDG 1 pattern in Western blot of glycoproteins associated with a deficient phosphomannomutase activity in blood leukocytes and compound heterozygosity in PMM2 gene. The sister of the father, who was also affected by PMM deficiency, presented with infertility and premature ovarian failure. Finally, the absence of any abnormal clinical or biological signs as for the case completes the clinical spectrum of PMM2-CDG at its extreme end, at the opposite of the supposed total lethality of the R141H homozygous status.
  JIMD reports. 01/2012; 5:123-5.
• Source

  Available from: Pascale Guicheney

  Article: Congenital muscular dystrophy type 1D (MDC1D) due to a large intragenic insertion/deletion, involving intron 10 of the LARGE gene.

  Nigel F Clarke, Svetlana Maugenre, Aurélie Vandebrouck, J Andoni Urtizberea, Tobias Willer, Rachel A Peat, Françoise Gray, Céline Bouchet, Hiroshi Manya, Sandrine Vuillaumier-Barrot, Tamao Endo, Eliane Chouery, Kevin P Campbell, André Mégarbané, Pascale Guicheney
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  ABSTRACT: Mutation of the LARGE gene is the rarest of the six known genetic causes of α-dystroglycanopathy. We report further a family with MDC1D due to a complex genomic rearrangement that was not apparent on standard sequencing of LARGE. Two sisters in a consanguineous family had moderate mental retardation and cerebellar malformations, together with dystrophic changes and markedly reduced α-dystroglycan glycosylation staining on muscle biopsy. There was homozygous linkage to the LARGE locus but sequencing of LARGE coding regions was normal. Analysis of LARGE cDNA showed an abnormal sequence inserted between exons 10 and 11, in most of the transcripts, predicted to introduce a premature stop codon. The abnormal sequence mapped to a spliced EST (DA935254) of unknown function, normally located at 100 kb centromeric of LARGE on chromosome 22q12.3. Quantitative PCR analysis of the EST and adjacent regions showed twice the normal copy number in patients' genomic DNA samples, consistent with a large intra-chromosomal duplication inserted into intron 10 of LARGE in a homozygous state. This insertion was associated with deletion of a central region of intron 10, but the exact break points of the deletion/duplication were not found, suggesting that an even more complex rearrangement may have occurred. The exact function of LARGE, a golgi protein, remains uncertain. POMT and POMGnT enzyme activities were normal in patients' lymphoblast cells, suggesting that defects in LARGE do not affect the initiation of O-mannosyl glycans.
  European journal of human genetics: EJHG 01/2011; 19(4):452-7. · 3.56 Impact Factor
• Article: POMT2 intragenic deletions and splicing abnormalities causing congenital muscular dystrophy with mental retardation.

  Akiko Yanagisawa, Céline Bouchet, Susana Quijano-Roy, Sandrine Vuillaumier-Barrot, Nigel Clarke, Sylvie Odent, Diana Rodriguez, Norma B Romero, Makiko Osawa, Tamao Endo, Ana Lia Taratuto, Nathalie Seta, Pascale Guicheney
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  ABSTRACT: Alpha-dystroglycanopathies are a group of congenital muscular dystrophies (CMDs) with autosomal recessive inheritance characterized by abnormal glycosylation of alpha-dystroglycan. Although six genetic causes have been identified (FKTN, POMGNT1, POMT1, POMT2, FKRP, and LARGE) many alpha-dystroglycanopathy patients remain without a genetic diagnosis after standard exon sequencing. To date POMT2 mutations have been identified in CMD cases with a wide range of clinical severities from Walker-Warburg syndrome to limb girdle muscular dystrophy without structural brain or ocular involvement. We analyzed POMT2 in six CMD patients, who had severe diffuse muscle weakness, generalized joint contractures, microcephaly, severe mental retardation and elevated CK levels. Eye involvement was absent or limited to myopia or strabismus. We sequenced the coding regions of POMT2 using genomic DNA and cDNA generated from blood lymphocytes or B lymphoblastoid cell lines. Quantitative PCR analysis of genomic DNA was used to identify and determine the breakpoints of large deletions. We report five novel mutations in POMT2, four of which were outside of coding exons, two large genomic deletions and two intronic single base substitutions that induced aberrant mRNA splicing. Large scale DNA rearrangements (such as large deletions) and cryptic splice mutations, that can be missed on standard sequencing of genomic DNA, may be relatively common in POMT2. Additional techniques, such as sequencing of cDNA are needed to identify all mutations. These results also confirm that POMT2 mutations are an important cause of the less severe alpha-dystroglycanopathy phenotypes.
  European journal of medical genetics 01/2009; 52(4):201-6. · 1.57 Impact Factor
• Article: Protein O-mannosyltransferase activities in lymphoblasts from patients with alpha-dystroglycanopathies.

  Hiroshi Manya, Céline Bouchet, Akiko Yanagisawa, Sandrine Vuillaumier-Barrot, Susana Quijano-Roy, Yasushi Suzuki, Svetlana Maugenre, Pascale Richard, Toshiyuki Inazu, Luciano Merlini, Norma B Romero, France Leturcq, Isabelle Bezier, Haluk Topaloglu, Brigitte Estournet, Nathalie Seta, Tamao Endo, Pascale Guicheney
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  ABSTRACT: Defects in O-mannosylation of alpha-dystroglycan cause some forms of congenital muscular dystrophy (CMD), the so-called alpha-dystroglycanopathies. Six genes are responsible for these diseases with overlapping phenotypes. We investigated the usefulness of a biochemical approach for the diagnosis and investigation of the alpha-dystroglycanopathies using immortalized lymphoblasts prepared from genetically diagnosed and undiagnosed CMD patients and from control subjects. We measured the activities of protein O-mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) and protein O-mannosyltransferase (POMT). Lymphoblasts from patients harbouring known mutations in either POMGNT1 or POMT1 showed a marked decrease in POMGnT1 or POMT activity, respectively, compared to controls. Furthermore, we identified pathogenic mutations in POMGNT1, POMT1 or POMT2 in six previously genetically uncharacterised patients who had very low enzyme activity. In conclusion, the lymphoblast-based enzymatic assay is a sensitive and useful method (i) to select patients harbouring POMGNT1, POMT1 or POMT2 mutations; (ii) to assess the pathogenicity of new or already described mutations.
  Neuromuscular Disorders 02/2008; 18(1):45-51. · 2.80 Impact Factor
• Article: A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings.

  Julia Dancourt, Sandrine Vuillaumier-Barrot, Helene Ogier de Baulny, Ignacio Sfaello, Anne Barnier, Christianne le Bizec, Thierry Dupre, Genevieve Durand, Nathalie Seta, Stuart E H Moore
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  ABSTRACT: Congenital disorders of glycosylation (CDG) type I (CDG I) are rare autosomal recessive diseases caused by deficiencies in the assembly of the dolichol-linked oligosaccharide (DLO) that is required for N-glycoprotein biosynthesis. CDG Ie is due to a defect in the synthesis of dolichyl-phosphoryl-mannose (Dol-P-Man), which is needed for DLO biosynthesis as well as for other glycosylation pathways. Human Dol-P-Man synthase is a heterotrimeric complex composed of DPM1p, DPM2p, and DPM3p, with DPM1p being the catalytic subunit. Here, we report two new CDG Ie patients who present milder symptoms than the five other CDG Ie patients described to date. The clinical pictures of the patients MS and his sister MT are dominated by major ataxia, with no notable hepatic involvement. MS cells accumulate the immature DLO species Dol-PP-GlcNAc2Man5 and possess only residual Dol-P-Man synthase activity. One homozygous intronic mutation, g.IVS4-5T>A, was found in the DPM1 gene, leading to exon skipping and transcription of a shortened transcript. Moreover, DPM1 expression was reduced by more than 90% in MS cells, in a nonsense-mediated mRNA decay (NMD)-independent manner. Full analysis of the DPM2 and DPM3 genes revealed a decrease in DPM2 expression and normal expression of DPM3. This description emphasizes the large spectrum of symptoms characterizing CDG I patients.
  Pediatric Research 07/2006; 59(6):835-9. · 2.70 Impact Factor
• Article: PMM2 intronic branch-site mutations in CDG-Ia.

  Sandrine Vuillaumier-Barrot, Christiane Le Bizec, Pascale De Lonlay, Nathalie Madinier-Chappat, Anne Barnier, Thierry Dupré, Geneviève Durand, Nathalie Seta
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  ABSTRACT: Congenital Disorders of Glycosylation (CDG, OMIM#212065)-Ia is an autosomal recessive disorder, characterized by central nervous system dysfunction and multiorgan failure associated with mutations in the PMM2 gene. We report two patients who are compound heterozygotes with respect to two new intronic mutations that affect a highly conserved adenosine in a consensus branch-site sequence. The mutations, one in intron 7: c.340 -23A > G (IVS7 -23A > G) and the other in intron 2: c.179 -25A > G (IVS2 -25A > G), are associated with the c.422G > A (R141H) and c.193 G > T (D65Y) mutations, respectively. The c.179 -25A > G and the c.340 -23A > G changes cause exon 3 and exon 8 to be lost at the RNA level, respectively. This kind of mutation can cause a problem in molecular diagnosis of CDG-Ia if intronic primers are not correctly chosen, and if molecular diagnosis is not performed at both the DNA and mRNA levels.
  Molecular Genetics and Metabolism 05/2006; 87(4):337-40. · 3.19 Impact Factor
• Article: A new insight into PMM2 mutations in the French population.

  Christiane Le Bizec, Sandrine Vuillaumier-Barrot, Anne Barnier, Thierry Dupré, Geneviève Durand, Nathalie Seta
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  ABSTRACT: Congenital disorder of Glycosylation type Ia is an autosomal recessive disorder, characterized by a central nervous system dysfunction and multiorgan failure associated with defective N-glycosylation and phosphomannomutase (PMM) deficiency related to mutations in the PMM2 gene (mRNA U85773.1, gene ID 5373). More than 75 different mutations have been previously described. In our study, 38 different mutations were found in 52 French families with CDG-Ia. Eleven mutations had not been previously published in CDG-Ia patients: eight missense and three splice mutations. We studied the PMM activity of eight novel recombinant mutant proteins in an E. coli expression system, comparing them with the wild type protein, c.422 G>A (R141H), and c.415 G>A (E139K) mutant proteins. We also studied the previously described c.590 C>A (E197A) found on the same allele as c.394 A>T (I132F). All mutant proteins studied except E197A had decreased activity and/or were thermolabile, and were pathogenic mutations. Haplotype studies revealed a founder effect for E139K mutation, only described in France and found in seven CDG-Ia families (7.6%). In contrast, at least two different haplotypes were observed for the R141H mutation in France, studied in 23 families. The R141H seems to be a combination of the "old" R141H mutation found all over Europe and a second "French" R141H, and could be substantially older than E139K.
  Human Mutation 05/2005; 25(5):504-5. · 5.69 Impact Factor
• Article: A deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation.

  Isabelle Chantret, Julia Dancourt, Thierry Dupré, Christophe Delenda, Stéphanie Bucher, Sandrine Vuillaumier-Barrot, Hélène Ogier de Baulny, Celine Peletan, Olivier Danos, Nathalie Seta, Geneviève Durand, Rafael Oriol, Patrice Codogno, Stuart E H Moore
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  ABSTRACT: The underlying causes of type I congenital disorders of glycosylation (CDG I) have been shown to be mutations in genes encoding proteins involved in the biosynthesis of the dolichyl-linked oligosaccharide (Glc(3)Man(9)GlcNAc(2)-PP-dolichyl) that is required for protein glycosylation. Here we describe a CDG I patient displaying gastrointestinal problems but no central nervous system deficits. Fibroblasts from this patient accumulate mainly Man(9)GlcNAc(2)-PP-dolichyl, but in the presence of castanospermine, an endoplasmic reticulum glucosidase inhibitor Glc(1)Man(9)GlcNAc(2)-PP-dolichyl predominates, suggesting inefficient addition of the second glucose residue onto lipid-linked oligosaccharide. Northern blot analysis revealed the cells from the patient to possess only 10-20% normal amounts of mRNA encoding the enzyme, dolichyl-P-glucose:Glc(1)Man(9)GlcNAc(2)-PP-dolichyl alpha3-glucosyltransferase (hALG8p), which catalyzes this reaction. Sequencing of hALG8 genomic DNA revealed exon 4 to contain a base deletion in one allele and a base insertion in the other. Both mutations give rise to premature stop codons predicted to generate severely truncated proteins, but because the translation inhibitor emetine was shown to stabilize the hALG8 mRNA from the patient to normal levels, it is likely that both transcripts undergo nonsense-mediated mRNA decay. As the cells from the patient were successfully complemented with wild type hALG8 cDNA, we conclude that these mutations are the underlying cause of this new CDG I subtype that we propose be called CDG Ih.
  Journal of Biological Chemistry 04/2003; 278(11):9962-71. · 4.77 Impact Factor
• Article: A Deficiency in Dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl α3-Glucosyltransferase Defines a New Subtype of Congenital Disorders of Glycosylation

  Isabelle Chantret, Julia Dancourt, Thierry Dupré, Christophe Delenda, Stéphanie Bucher, Sandrine Vuillaumier-Barrot, Hélène Ogier de Baulny, Céline Peletan, Olivier Danos, Nathalie Seta, Geneviève Durand, Rafael Oriol, Patrice Codogno, Stuart E. H. Moore
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  ABSTRACT: The underlying causes of type I congenital disorders of glycosylation (CDG I) have been shown to be mutations in genes encoding proteins involved in the biosynthesis of the dolichyl-linked oligosaccharide (Glc3Man9GlcNAc2-PP-dolichyl) that is required for protein glycosylation. Here we describe a CDG I patient displaying gastrointestinal problems but no central nervous system deficits. Fibroblasts from this patient accumulate mainly Man9GlcNAc2-PP-dolichyl, but in the presence of castanospermine, an endoplasmic reticulum glucosidase inhibitor Glc1Man9GlcNAc2-PP-dolichyl predominates, suggesting inefficient addition of the second glucose residue onto lipid-linked oligosaccharide. Northern blot analysis revealed the cells from the patient to possess only 10–20% normal amounts of mRNA encoding the enzyme, dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl α3-glucosyltransferase (hALG8p), which catalyzes this reaction. Sequencing of hALG8 genomic DNA revealed exon 4 to contain a base deletion in one allele and a base insertion in the other. Both mutations give rise to premature stop codons predicted to generate severely truncated proteins, but because the translation inhibitor emetine was shown to stabilize the hALG8 mRNA from the patient to normal levels, it is likely that both transcripts undergo nonsense-mediated mRNA decay. As the cells from the patient were successfully complemented with wild type hALG8cDNA, we conclude that these mutations are the underlying cause of this new CDG I subtype that we propose be called CDG Ih.
  Journal of Biological Chemistry 03/2003; 278(11):9962-9971. · 4.77 Impact Factor
• Article: Leukocyte phosphomannomutase activity in diagnosis of congenital disorder of glycosylation Ia.

  Anne Barnier, Thierry Dupré, Maryvonne Cuer, Sandrine Vuillaumier-Barrot, Geneviève Durand, Nathalie Seta
  Clinical Chemistry 07/2002; 48(6 Pt 1):934-6. · 7.91 Impact Factor
• Article: Involvement of renin-angiotensin system in pressure-flow relationship: role of angiotensin-converting enzyme gene polymorphism.

  Sigismond Lasocki, Marc Iglarz, Pierre-François Seince, Sandrine Vuillaumier-Barrot, Eric Vicaut, Daniel Henrion, Bernard Levy, Jean-Marie Desmonts, Ivan Philip, Joelle Bénessiano
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  ABSTRACT: The renin-angiotensin system is involved in blood pressure regulation. The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is known to be associated with variation of plasma and cellular ACE concentrations. Furthermore, changes in arterial function have been suggested to be associated to the DD genotype. The aim of the study was to investigate the arterial vascular response to a physiologic stimulus (i.e., flow) according to the I/D ACE gene polymorphism. Sixty patients scheduled for coronary artery bypass grafting (n = 24) or valve surgery (n = 36) under normothermic cardiopulmonary bypass were genotyped in a blind manner by polymerase chain reaction. Mean arterial pressure was measured at pump flows ranging from 1 to 3 l x min(-1) x m (-2) by 0.25 l x min(-1) x m(-2) step each 15 s, to obtain a pressure-flow relation. Independent factors associated with the variation of the slope of the pressure-flow relation curve were assessed by multivariate analysis. We found a D allelic frequency of 0.54. Patients were separated in two groups (DD, n = 16; ID/II, n = 44). There were no significant difference with regard to preoperative and intraoperative data between the two groups. DD patients had their pressure-flow relation curves shifted upward (with higher pressures as flow increased), indicating a lesser decrease in vascular resistance. Furthermore, DD genotype was the only independent predictor of the slope of the curves (21.5 +/- 4.2 vs. 18.1 +/- 5 mmHg/[l x min(-1) x m(-2)] for DD and ID/II, respectively; P = 0.02; values are mean +/-SD). These results show that vasomotor properties are influenced by the I/D polymorphism of the ACE gene.
  Anesthesiology 03/2002; 96(2):271-5. · 5.36 Impact Factor
• Article: Preproendothelin-1 gene polymorphism is related to a change in vascular reactivity in the human mammary artery in vitro.

  Marc Iglarz, Joëlle Benessiano, Ivan Philip, Sandrine Vuillaumier-Barrot, Sigismond Lasocki, Ulrich Hvass, Geneviève Durand, Jean-Marie Desmonts, Bernard I Lévy, Daniel Henrion
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  ABSTRACT: A gene polymorphism of preproendothelin-1 (a G-to-T transversion that predicts a Lys/Asn change at codon 198) associated with an increased risk of hypertension has been recently described in patients carrying the T allele. No study has yet determined the impact of this polymorphism on vascular reactivity, although a functional role for endothelin-1 in the pathophysiology of hypertension has been clarified. At subthreshold concentrations, endothelin-1 and angiotensin II induce a potentiation of alpha-adrenergic-dependent vascular tone caused by an increased sensitivity of the contractile apparatus to calcium. We investigated phenylephrine-induced tone and its amplification by endothelin-1 and angiotensin II in human mammary artery rings in vitro. Contractions to phenylephrine (0.1 to 100 micromol) and endothelin-1 (0.1 to 300 nmol) were not significantly different in rings from GT/TT (n=27) and GG (n=21) patients. A subthreshold concentration of endothelin-1 (10 pmol) potentiated a phenylephrine-induced contraction (eg, 44 +/- 12% increase in tone with phenylephrine 1 micromol/L, P<0.001) that was significantly higher in the GT/TT group than in the GG group (eg, 44 +/- 12% versus 82 +/- 11%, P<0.01). A similar effect on response to phenylephrine was observed with a subthreshold concentration of angiotensin II. We also found a higher response to calcium in arteries from GT/TT patients. Endothelium-dependent or -independent relaxations were unaffected by the genotype. These data suggest that the preproendothelin-1 gene polymorphism is associated with a higher potentiating effect of endothelin-1 and angiotensin II, probably in relation with higher calcium sensitivity. These changes in vascular reactivity might help to understand the relations between this polymorphism and cardiovascular disorders.
  Hypertension 03/2002; 39(2):209-13. · 6.21 Impact Factor
• Article: Should PMM2-deficiency (CDG Ia) be searched in every case of unexplained hydrops fetalis?

  Nadia Léticée, Bettina Bessières-Grattagliano, Thierry Dupré, Sandrine Vuillaumier-Barrot, Pascale de Lonlay, Ferechté Razavi, Nadia El Khartoufi, Yves Ville, Michel Vekemans, Raymonde Bouvier, Nathalie Seta, Tania Attié-Bitach
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  ABSTRACT: Hydrops fetalis (HF) is characterized by an accumulation of fluid in the extracellular compartments and in body cavities. Non-immune HF (NIHF) is caused by a wide variety of disorders and overall, 20-25% of NIHF remain unexplained. Inborn errors of metabolism, mostly lysosomal storage diseases have been estimated to account for 1-2% of cases, leading to HF by anemia or liver failure. Very few cases of NIHF and Congenital Disorder of Glycosylation (CDG) have been reported. We present here a case of recurrence of HF in a non-related couple in which the diagnosis of CDG type I was suspected at fetal pathological examination then confirmed at the enzymatic and molecular levels, as well as on a characteristic CDG I serum transferrin profile at 30weeks of gestation. We also provide a systematic review of reported cases with CDG type I and NIHF reported thus far. When NIHF remains unexplained despite exhaustive obstetrical screening, analysis of PMM activity in the parents' leucocytes is possible and might be performed easily during pregnancy. The accurate diagnosis is important in terms of counseling during pregnancy or later, in order to allow an early molecular prenatal diagnosis for the following pregnancies.
  Molecular Genetics and Metabolism 101(2-3):253-7. · 3.19 Impact Factor