Michel Roussey

Publications (28)93.67 Total impact

• Article: CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders.

  Christel Thauvin-Robinet, Anne Munck, Frédéric Huet, Alix de Becdelièvre, Clément Jimenez, Guy Lalau, Elodie Gautier, Jacques Rollet, Jean Flori, Raphaëlle Nové-Josserand, [......], Catherine Costa, Véronique Drouineaud, Patricia Fauque, Christine Binquet, Claire Bonithon-Kopp, Mike A Morris, Laurence Faivre, Michel Goossens, Michel Roussey, Emmanuelle Girodon
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma. METHODS: Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics. RESULTS: 97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166/179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation. CONCLUSIONS: Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD.
  Journal of Medical Genetics 02/2013; · 6.36 Impact Factor
• Article: Cascade testing in families of carriers identified through newborn screening in Western Brittany (France).

  Ingrid Duguépéroux, Marie-Pierre Audrézet, Philippe Parent, Séverine Audebert-Bellanger, Michel Roussey, Claude Férec, Virginie Scotet
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) can lead to the detection of healthy carriers. We report a unique assessment of family testing following the identification of carriers by NBS for over 20years, in an area where CF is frequent. METHODS: We reviewed all of the carriers identified by NBS between 1991 and 2010 and registered the tests done in those families. RESULTS: NBS identified 0.1% of the newborns as carriers, which correspond only to 2.6% of the expected carriers born within the period, and 1/3 of those with an increased IRT level. Of the 195 families, 75.9% requested testing (2.5 tests per family). We identified 183 carriers and five 1-in-4 risk couples. Reassurance about genetic status was provided to 96% of the couples. CONCLUSIONS: Carriers detected by NBS appeared to be well managed in our area, and cascade testing that informs on genetic status seems relatively active.
  Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 12/2012; · 3.19 Impact Factor
• Article: [Abuse and children at risk: why recognize, how to support?].

  Martine Balençon, Anne Drénou, Michel Roussey
  La Revue du praticien 06/2012; 62(6):819-20.
• Source

  Available from: PubMed Central

  Article: Evidence for decline in the incidence of cystic fibrosis: a 35-year observational study in Brittany, France.

  Virginie Scotet, Ingrid Duguépéroux, Philippe Saliou, Gilles Rault, Michel Roussey, Marie-Pierre Audrézet, Claude Férec
  [show abstract] [hide abstract]
  ABSTRACT: Cystic fibrosis (CF) is an autosomal recessive disorder whose incidence has long been estimated as 1/2500 live births in Caucasians. Expanding implementation of newborn screening (NBS) programs now allows a better monitoring of the disease incidence, what is essential to make reliable predictions for disease management. This study assessed time trends in the birth incidence of CF over a long period (35 years: 1975-2009) in an area where CF is frequent (Brittany, France) and where NBS has been implemented for more than 20 years. This study enrolled CF patients born in Brittany between January 1st 1975 and December 31st 2009 (n = 483). Time trends in incidence were examined using Poisson regression and mainly expressed using the average percent change (APC). The average number of patients born each year declined from 18.6 in the late 1970's (period 1975-79) to 11.6 nowadays (period 2005-09). The corresponding incidence rates dropped from 1/1983 to 1/3268, which represented a decline close to 40% between these two periods (APC = -39.3%, 95% CI = -55.8% to -16.7%, p = 0.0020). A clear breakpoint in incidence rate was observed at the end of the 1980's (p < 0.0001). However, the incidence rate has remained quite stable since that time (annual APC = -1.0%, 95% CI = -3.0% to 1.1%, p = 0.3516). This study provides an accurate picture of the evolution of the incidence of a genetic disease over a long period and highlights how it is influenced by the health policies implemented. We observed a 40% drop in incidence in our area which seems consecutive to the availability of prenatal diagnosis.
  Orphanet Journal of Rare Diseases 03/2012; 7:14. · 5.83 Impact Factor
• Article: Newborn screening programmes including genetic analyses: limits and risks of negative consequences?

  Christel Thauvin-Robinet, Anne Munck, Michel Roussey, Frédéric Huet, Christine Binquet, Emmanuelle Girodon
  Journal of epidemiology and community health 11/2010; 64(11):937-8. · 3.04 Impact Factor
• Article: Clinical phenotype and genotype of children with borderline sweat test and abnormal nasal epithelial chloride transport.

  Isabelle Sermet-Gaudelus, Emanuelle Girodon, Dorota Sands, Nathalie Stremmler, Vera Vavrova, Eric Deneuville, Philippe Reix, Stéphanie Bui, Frédéric Huet, Muriel Lebourgeois, [......], Veronika Skalicka, Thierry Bienvenu, Delphine Roussel, Gérard Lenoir, Gabriel Bellon, Jacques Sarles, Milan Macek, Michel Roussey, Isabelle Fajac, Aleksander Edelman
  [show abstract] [hide abstract]
  ABSTRACT: The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with a sweat chloride (Cl(-)) concentration greater than 60 mmol/L or the identification of two CF-causing mutations. A challenging problem is the significant number of children for whom no definitive diagnosis is possible because they present with symptoms suggestive of CF, a sweat chloride level in the intermediate range between 30 and 60 mmol/L, and only one or no identified CF-causing mutation. To investigate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways of children with intermediate sweat tests and inconclusive genetic findings in correlation with clinical phenotype and genotype. We developed a composite nasal potential difference (NPD) diagnostic score to discriminate patients with CF from non-CF patients. We tested NPD in 50 children (age, 6 mo to 18 yr) with equivocal diagnoses and correlated the NPD diagnostic score with clinical phenotypes and genotypes. Fifteen of the 50 children had NPD scores in the CF range. Eight of the 15 carried two CFTR mutations compared with only 5 of the 35 children with normal NPD scores (P = 0.01). They were significantly younger at evaluation and had recurrent lower respiratory tract infections, chronic productive coughs, and chronic Staphylococcus aureus colonization significantly more often than the 35 children with normal NPD results. Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.
  American Journal of Respiratory and Critical Care Medicine 10/2010; 182(7):929-36. · 11.08 Impact Factor
• Article: Measurement of nasal potential difference in young children with an equivocal sweat test following newborn screening for cystic fibrosis.

  Isabelle Sermet-Gaudelus, Emmanuelle Girodon, Delphine Roussel, Eric Deneuville, Stéphanie Bui, Frédéric Huet, Marcel Guillot, Rola Aboutaam, Michel Renouil, Anne Munck, Marie des Georges, Albert Iron, Christel Thauvin-Robinet, Isabelle Fajac, Gerard Lenoir, Michel Roussey, Aleksander Edelman
  [show abstract] [hide abstract]
  ABSTRACT: A challenging problem arising from cystic fibrosis (CF) newborn screening is the significant number of infants with hypertrypsinaemia (HIRT) with sweat chloride levels in the intermediate range and only one or no identified CF-causing mutations. To investigate the diagnostic value for CF of assessing CF transmembrane conductance regulator (CFTR) protein function by measuring nasal potential difference in children with HIRT. A specially designed protocol was used to assess nasal potential difference (NPD) in 23 young children with HIRT (3 months-4 years) with inconclusive neonatal screening. Results were analysed with a composite score including CFTR-dependent sodium and chloride secretion. Results were correlated with genotype after extensive genetic screening and with clinical phenotype at follow-up 3 years later. NPD was interpretable for 21 children with HIRT: 13 had NPD composite scores in the CF range. All 13 were finally found to carry two CFTR mutations. At follow-up, nine had developed a chronic pulmonary disease consistent with a CF diagnosis. The sweat test could be repeated in nine children, and six had sweat chloride values >or=60 mmol/l. Of the eight children with normal NPD scores, only two had two CFTR mutations, both wide-spectrum mutations. None had developed a CF-like lung disease at follow-up. The sweat test could be reassessed in five of these eight children and all had sweat chloride values <60 mmol/l. CF diagnosis was ruled out in six of these eight children. Evaluation of CFTR function in the nasal epithelium of young children with inconclusive results at CF newborn screening is a useful diagnostic tool for CF.
  Thorax 06/2010; 65(6):539-44. · 6.84 Impact Factor
• Article: Psychological effects of false-positive results in cystic fibrosis newborn screening: a two-year follow-up.

  Julie Beucher, Emmanuelle Leray, Eric Deneuville, Monique Roblin, Isabelle Pin, François Bremont, Dominique Turck, Jean-Louis Giniès, Pascal Foucaud, Gilles Rault, Jocelyne Derelle, Valérie David, Hubert Journel, Sophie Marchand, David Veillard, Michel Roussey
  [show abstract] [hide abstract]
  ABSTRACT: To evaluate parental stress after a false-positive result at the time of the cystic fibrosis (CF) newborn screening (NBS), attributable to heterozygotism or persistent hypertrypsinemia. A prospective study was conducted in 86 French families at 3, 12, and 24 months after NBS. A psychologist conducted interviews with a questionnaire, the Perceived Stress Scale, and the Vulnerable Child Scale. Overall, 96.5% of parents said they had been anxious at the time of the sweat test. However, 86% felt entirely reassured 3 months after the test. The mean Perceived Stress Scale score did not differ from that observed in the French population. Mean Vulnerable Child Scale scores were high, associated with a low Parental Perception of Child Vulnerability. These results did not differ significantly at 1 and 2 years. In total, 86% to 100% of families no longer worried about CF. All parents stated that they would have the test performed again for another child. CF NBS can lead to false-positive results, causing parental anxiety, which quickly decreases after a sweat test performed soon after the phone call.
  The Journal of pediatrics 02/2010; 156(5):771-6, 776.e1. · 4.02 Impact Factor
• Article: The importance of sweat testing for older siblings of patients with cystic fibrosis identified by newborn screening.

  Anne Munck, Elise Houssin, Michel Roussey
  [show abstract] [hide abstract]
  ABSTRACT: We report cystic fibrosis (CF) care center instructions for sweat testing in older siblings after implementation of the French nationwide newborn screening program, and we evaluate the incidence of unrecognized CF. Nearly 9% of families with an infant screened for CF were unaware of an affected older sibling. We strongly recommend sweat testing for all first-degree older children.
  The Journal of pediatrics 12/2009; 155(6):928-930.e1. · 4.02 Impact Factor
• Article: Pulmonary outcome differences in U.S. and French cystic fibrosis cohorts diagnosed through newborn screening.

  Aimee C Walsh, Gilles Rault, Zhanhai Li, Virginie Scotet, Ingrid Duguépéroux, Claude Férec, Michel Roussey, Anita Laxova, Philip M Farrell
  [show abstract] [hide abstract]
  ABSTRACT: A comparison of the longitudinal progression of lung disease in cystic fibrosis patients identified through newborn screening (NBS) in cohorts located in two different countries has never been performed and was the primary objective of this study. The study included 56 patients in Brittany diagnosed through NBS between 1989 and 1994 and 69 similar patients in Wisconsin between 1985 and 1994. The onset and progression of lung disease was radiographically quantified using the Wisconsin Chest X-ray (WCXR) scoring system. A single pediatric pulmonologist blinded to all identifiers scored the films. Generalized estimating equation analyses adjusted for age, genotype, sex, pancreatic insufficiency, and meconium ileus showed worse WCXR scores in Brittany patients compared to Wisconsin patients (average score difference=4.48; p<0.001). Percent predicted FEV1 was also worse among Brittany patients (p<0.001). The finding of milder radiographically-quantified lung disease using the WCXR scoring system, as well as better FEV1 values, may be explained by variations in nutrition, environmental exposures, or healthcare delivery.
  Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 11/2009; 9(1):44-50. · 3.19 Impact Factor
• Article: [Psychomotor development of infants and children].

  Estelle Breton, Michel Roussey
  La Revue du praticien 07/2009; 59(6):841-2.
• Article: Role of congenital long-QT syndrome in unexplained sudden infant death: proposal for an electrocardiographic screening in relatives.

  Alban-Elouen Baruteau, Julien Baruteau, Ryad Joomye, Raphael Martins, Frédéric Treguer, Remi Baruteau, Jean-Claude Daubert, Philippe Mabo, Michel Roussey
  [show abstract] [hide abstract]
  ABSTRACT: INTRODUCTION: Congenital long-QT syndrome (LQTS) is a sporadic or familial inherited arrhythmia. It can lead to sudden death by ventricular fibrillation which occurs at any age but particularly during infancy. Recent studies of postmortem molecular analysis in infants who died of unexplained sudden infant death syndrome (SIDS) showed abnormal mutations to LQTS in 10% to 12%. Current methods of etiologic investigation of sudden infant death syndrome do not allow the diagnosis of LQTS. A targeted anamnesis together with systematic electrocardiograms of first- and second-degree relatives could be an efficient LQTS diagnostic tool. Therefore, we propose to include them in screening procedures for SIDS etiologies. CONCLUSION: LQTS accounts for a significant number of unexplained SIDS. We suggest adding a systematic familial electrocardiographic screening to the current etiologic investigations in order to track congenital LQTS in relatives.
  European Journal of Pediatrics 04/2009; 168(7):771-7. · 1.88 Impact Factor
• Article: Screening to detect permanent childhood hearing impairment in neonates transferred from the newborn nursery.

  René Dauman, Michel Roussey, Véronique Belot, Françoise Denoyelle, Stéphane Roman, Isabelle Gavilan-Cellié, Isabelle Ruzza-Surroca, Marie-Noëlle Calmels, Geneviève Lina-Granade, Elise Houssin, Agnès Charlemagne, Noël Garabedian
  [show abstract] [hide abstract]
  ABSTRACT: The focus of this report is hearing screening of newborns transferred from the regular nursery to a specialized area. The purpose of the study undertaken was: (1) to determine whether screening coverage in this population was achieved; (2) to establish whether the linkage between neonatal screening and the diagnostic follow-up was carried out correctly; (3) to better determine the incidence of permanent childhood hearing impairment (PCHI) in this at-risk population. Six population centres averaging 12,000 births annually participated (Bordeaux, Lille, Paris, Marseille, Toulouse and Lyon). Automated auditory brainstem response (AABR) (Natus ALGO 3i) screening was performed in two stages: i.e. infants with initial "positive" results were screened a second time using the same technique. Of the 117,103 babies born during the study period, 4972 neonates were "transferred" and comprised the population for this report (4.2% of the total births). Screening results for 4972 "transferred" neonates were compared with those of non-transferred neonates (N=112,131). Screening coverage of eligible infants was significantly lower (75.4%) in "transferred" neonates (3750 infants screened) compared to 97.5% coverage of non-transferred neonates (109,349 infants screened). The rate of positive results after the first stage AABR was higher in the "transferred" population (11.1%) than in the non-transferred population (6.5%). Of the 415 "transferred" newborns with initial positive screens, 91.3% were rechecked as stipulated in the project protocol. The second pre-discharge AABR ascertained that in half of the cases auditory function had normalized in the day. Of the 183 "transferred" infants whose result remained suspect at the conclusion of both stages of the neonatal screen (4.9% of the tested population), only 70.5% returned to the audiology centre for diagnostic follow-up. The incidence of bilateral PCHI was markedly higher (4/1000) in "transferred" infants than in the non-transferred population (1.08/1000). The difficulty of obtaining universal screening coverage in "transferred" infants was, unfortunately, verified in this prospective, multicentre study. Further, the diversity of our "transferred" population was not much greater than that revealed by careful analysis of published hearing screening studies in neonatal intensive care unit (NICU) infants. The influence of risk factors and their more or less complex combinations is apparent.
  International journal of pediatric otorhinolaryngology 02/2009; 73(3):457-65. · 0.85 Impact Factor
• Article: [Child abused and neglect. Maternal and child protection].

  Martine Balençon, Michel Roussey
  La Revue du praticien 10/2008; 58(13):1463-8.
• Article: Pancreatic enzyme replacement therapy for young cystic fibrosis patients.

  Anne Munck, Jean-Francois Duhamel, Thierry Lamireau, Bernard Le Luyer, Claire Le Tallec, Gabriel Bellon, Michel Roussey, Pierre Foucaud, Jean Louis Giniès, Anne Houzel, Christophe Marguet, Marcel Guillot, Valerie David, Nathalie Kapel, François Dyard, Friederike Henniges
  [show abstract] [hide abstract]
  ABSTRACT: Maldigestion in cystic fibrosis (CF) affects approximately 90% of patients. As soon as pancreatic insufficiency is identified, enzyme supplementation is prescribed even with breast fed infants. A pancreatic enzyme preparation developed particularly for infants, Creon for children (CfC), contains smaller granules to be administered with a dosing spoon (5000 lipase units per scoop). In a prospective, randomised, multi-centre study, 40 infants and toddlers received both CfC and Creon 10000 (C10) for two weeks each in a cross-over design. Dosing of pancreatic enzymes was continued as applied before the study. The primary endpoint was the parents' treatment preference. Secondary endpoints included coefficient of fat absorption (CFA), clinical symptoms and safety parameters. 20 parents (51%) from the N=39 intent to treat sample preferred CfC, 9 (23%) preferred C10, and 10 (26%) had no preference The applied doses led to a mean CFA with similar results for both treatments (77.8% vs. 78.7%). Gastrointestinal symptoms were reported on a number of study days, and some children had abnormal results for laboratory parameters of malabsorption. Safety and tolerability of the preparations were good and all these parameters were comparable for both treatments. Those parents who had a preference favoured CfC over C10. Both enzyme preparations improved malabsorption to a similar degree, although the applied dosages could have been too low in some children reflected in a suboptimal CFA. These data support the use of CfC for young patients with cystic fibrosis improving the daily care of this cohort detected mainly now through neonatal screening programmes.
  Journal of Cystic Fibrosis 09/2008; 8(1):14-8. · 3.19 Impact Factor
• Article: Implementation of the French nationwide cystic fibrosis newborn screening program.

  Anne Munck, Jean-Louis Dhondt, Camille Sahler, Michel Roussey
  [show abstract] [hide abstract]
  ABSTRACT: To describe optimization of a nationwide newborn screening program for cystic fibrosis (CF) that combines an immunoreactive trypsinogen (IRT) assay and DNA mutation analysis in dried blood samples at day 3. Data from regional screening laboratories and CF care centers were centralized and periodically analyzed to allow adaptation, thus limiting the number of false-positive cases. A total of 2717905 infants were screened between 2002 and 2005. Flow chart protocol was modified twice. First, the IRT d3 cutoff value increased from 60 to 65 microg/L, thus decreasing the percentage of samples requiring mutation analysis from 0.82% to 0.64%. Second, for infants with no mutations using the screening panel, a recall for IRT was performed only if IRT d3 was > 100 microg/L; the percentage of recalls decreased from 0.51% to 0.12%, and the percentage of infants requiring a sweat test decreased from 0.14% to 0.01%. No significant change in the CF detection rate was observed after these 2 modifications. A total of 625 CF cases were detected, and 22 false-negative findings (3.4%) were observed, most of them inevitable, with a low initial IRT. The centralized data analysis led to changes in the screening strategy to optimise the newborn screening program.
  The Journal of pediatrics 09/2008; 153(2):228-33, 233.e1. · 4.02 Impact Factor
• Article: [Life threatening event and sudden infant death].

  Estelle Breton, Michel Roussey
  La Revue du praticien 06/2008; 58(9):1003-7.
• Article: [National ranking exam. N29. What could happen at the exam?].

  Isabelle Granier, Michel Roussey
  La Revue du praticien 12/2006; 56(17):1925-6.
• Article: Immunoreactive trypsin/DNA newborn screening for cystic fibrosis: should the R117H variant be included in CFTR mutation panels?

  Virginie Scotet, Marie-Pierre Audrézet, Michel Roussey, Gilles Rault, Anne Dirou-Prigent, Hubert Journel, Valérie Moisan-Petit, Véronique Storni, Claude Férec
  [show abstract] [hide abstract]
  ABSTRACT: Cystic fibrosis newborn screening is now implemented universally in France, as well as in many states in the United States and in various areas of Europe and Australia. Because the screening protocol usually includes the analysis of the most common CFTR mutations, it is of the utmost importance that only mutations that result in classical cystic fibrosis are included in this test. The panels of mutations used in most cystic fibrosis newborn screening programs enable the detection of a relatively frequent CFTR variant (R117H) whose implication in cystic fibrosis remains unclear. Physicians, therefore, have difficulty managing detected compound heterozygotes with this variant, which raises the issue of the appropriateness of extended testing in families and of the legitimate use of prenatal diagnosis. The aim of this study was to describe the clinical outcome of the children found to be compound heterozygous for R117H by screening in Brittany (western France), where cystic fibrosis newborn screening was set up in 1989, and to assess whether this CFTR variant should be included in the newborn screening mutation panels. Data on clinical status were obtained by the referring pediatricians. Since our screening protocol has enabled detection of R117H (ie, in 1995), 360466 newborns have been screened for cystic fibrosis in Brittany, of whom 124 had elevated immunoreactive trypsin and 2 mutations in the CFTR gene. Nine of these children (7.3%) were compound heterozygous for R117H, which in all cases was linked to the 7T_11TG haplotype [IVS8-nT variant/m(TG) repeat]. Their genotypes were F508del/R117H (n = 7), I507del/R117H (n = 1), or G551D/R117H (n = 1). At the time of this writing, the mean age of these 9 children was 7.0 years (the oldest being >10 years of age), and none of them had yet developed any signs of cystic fibrosis; they have been pancreatic sufficient and have had good nutritional status and pulmonary function. Moreover, we observed that, in Brittany, all the patients carrying the R117H variant have been identified exclusively through cystic fibrosis newborn screening. In view of the high frequency of R117H-7T identified by cystic fibrosis newborn screening, the uncertain outcome of the asymptomatic children, and physicians' difficulty in managing these situations, we propose the withdrawal of the R117H variant from the panels of CFTR mutations used in cystic fibrosis newborn screening, given the expanding implementation of cystic fibrosis newborn screening.
  PEDIATRICS 11/2006; 118(5):e1523-9. · 4.47 Impact Factor
• Article: [Psychomotor development and infants and children].

  Isabelle Granier, Michel Roussey
  La Revue du praticien 03/2006; 56(4):445-54.