Publications by authors named "Isabelle Guemas"

4 Publications

  • Page 1 of 1

Increasing knowledge in defects: lessons from 35 new patients.

J Med Genet 2020 03 5;57(3):160-168. Epub 2019 Oct 5.

Sorbonne Université, UFR Médecine, Paris, France.

Background: The type 1 insulin-like growth factor receptor (IGF1R) is a keystone of fetal growth regulation by mediating the effects of IGF-I and IGF-II. Recently, a cohort of patients carrying an defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified defects, as no external validation was available. Furthermore, we aimed to develop a functional test to allow the classification of variants of unknown significance (VUS) in vitro.

Methods: DNA was tested for either deletions or single nucleotide variant (SNV) and the phosphorylation of downstream pathways studied after stimulation with IGF-I by western blot analysis of fibroblast of nine patients.

Results: We detected 21 defects in 35 patients, including 8 deletions and 10 heterozygous, 1 homozygous and 1 compound-heterozygous SNVs. The main clinical characteristics of these patients were being born small for gestational age (90.9%), short stature (88.2%) and microcephaly (74.1%). Feeding difficulties and varying degrees of developmental delay were highly prevalent (54.5%). There were no differences in phenotypes between patients with deletions and SNVs of . Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation.

Conclusion: We report eight new pathogenic variants of and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of defects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
March 2020

Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case-control study.

F Balazard S Le Fur S Valtat A J Valleron P Bougnères Dominique Thevenieau Corinne Fourmy Chatel Rachel Desailloud Hélène Bony-Trifunovic Pierre-Henri Ducluzeau Régis Coutant Sophie Caudrelier Armelle Pambou Emmanuelle Dubosclard Florence Joubert Philippe Jan Estelle Marcoux Anne-Marie Bertrand Brigitte Mignot Alfred Penformis Chantal Stuckens Régis Piquemal Pascal Barat Vincent Rigalleau Chantal Stheneur Sylviane Fournier Véronique Kerlan Chantal Metz Anne Fargeot-Espaliat Yves Reznic Frédérique Olivier Iva Gueorguieva Arnaud Monier Catherine Radet Vincent Gajdos Daniel Terral Christine Vervel Djamel Bendifallah Candace Ben Signor Daniel Dervaux Abdelkader Benmahammed Guy-André Loeuille Françoise Popelard Agnès Guillou Pierre-Yves Benhamou Jamil Khoury Jean-Pierre Brossier Joachim Bassil Sylvaine Clavel Bernard Le Luyer Pierre Bougnères Françoise Labay Isabelle Guemas Jacques Weill Jean-Pierre Cappoen Sylvie Nadalon Anne Lienhardt-Roussie Anne Paoli Claudie Kerouedan Edwige Yollin Marc Nicolino Gilbert Simonin Jacques Cohen Catherine Atlan Agnès Tamboura Hervé Dubourg Marie-Laure Pignol Philippe Talon Stéphanie Jellimann Lucy Chaillous Sabine Baron Marie-Noëlle Bortoluzzi Elisabeth Baechler Randa Salet Ariane Zelinsky-Gurung Fabienne Dallavale Etienne Larger Marie Laloi-Michelin Jean-François Gautier Bénédicte Guérin Laure Oilleau Laetitia Pantalone Céline Lukas Isabelle Guilhem Marc De Kerdanet Marie-Claire Wielickzo Mélanie Priou-Guesdon Odile Richard François Kurtz Norbert Laisney Déborah Ancelle Guilhem Parlier Catherine Boniface Dominique Paris Bockel Denis Dufillot Berthe Razafimahefa Pierre Gourdy Pierre Lecomte Myriam Pepin-Donat Marie-Emmanuelle Combes-Moukhovsky Brigitte Zymmermann Marina Raoulx Anne Gourdin Et Catherine Dumont

BMC Public Health 2016 Sep 29;16(1):1021. Epub 2016 Sep 29.

INSERM U1169, Hôpital Bicêtre, Université Paris-Sud, Kremlin-Bicêtre, France.

Background: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D.

Methods: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods.

Results: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age.

Conclusions: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas.

Trial Registration: NCT02212522 . Registered August 6, 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
September 2016

New cases of isolated congenital central hypothyroidism due to homozygous thyrotropin beta gene mutations: a pitfall to neonatal screening.

Thyroid 2010 Jun;20(6):639-45

Centre des Maladies Endocriniennes Rares de la Croissance, Hôpital Necker Enfants-Malade, Assistance Publique-Hôpitaux de PARIS, Institut National de la Santé et de la Recherche Médicale U845 and Pediatric Endocrine Unit, Université Paris Descartes, Paris, France.

Background: Congenital central hypothyroidism (CCH) is a rare condition that is often diagnosed in late childhood in countries where neonatal screening programs rely solely on detecting thyrotropin (TSH) elevation. TSHbeta gene mutation is one of the causes of CCH. We describe two cases of c.Q49X mutation and three cases of c.C105Vfs114X mutation in exon 3 of the TSH beta-subunit gene.

Summary: We found two different TSHbeta gene mutations in two families. In one family, we identified a missense mutation in exon 3 leading to a premature stop at position 49 (c.Q49X) in the two affected twins. In the other family, the three affected siblings had a 313delT nucleotide deletion leading to a frame shift responsible for premature termination at codon 114 (c.C105Vfs114X); neonatal screening showed very low TSH levels in all three patients. The presence of inappropriately low TSH levels at birth in the three affected members of the second family raises questions about the value of the TSH level for CCH screening.

Conclusions: The marked phenotypic variability in patients with the c.Q49X mutation suggests modulation by interacting genes and/or differences in the genetic background. TSHbeta gene mutations should be suspected in neonates with inappropriately low TSH levels.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
June 2010

Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1).

Mol Cell Endocrinol 2006 Jul 6;254-255:78-83. Epub 2006 Jun 6.

Assistance Publique Hôpitaux de Paris, Robert Debre Hospital Paediatric Endocrinology unit, Robert Debré Hospital, Paris, France.

Kallmann syndrome characterised by hypogonadotropic hypogonadism (HH) and anosmia is genetically heterogeneous with X-linked, autosomal dominant and autosomal recessive forms. The autosomal dominant form due to loss of function mutation in the fibroblast growth factor receptor 1 (FGFR1) accounts for about 10% of cases. We report here three paediatric cases of Kallmann syndrome with unusual phenotype in two unrelated patients with severe ear anomalies (hypoplasia or agenesis of external ear) associated with classical features, such as cleft palate, dental agenesis, syndactylia, micropenis and cryptorchidism. We found de novo mutation in these two patients (Cys178Ser and Arg622Gly, respectively), and one inherited Arg622Gln mutation with intrafamilial variable phenotype. These genotype-phenotype correlations indicate that paediatric phenotypic expression of FGFR1 loss of function mutations is highly variable, the severity of the oro-facial malformations at birth does not predict gonadotropic function at the puberty and that de novo mutations of FGFR1 are relatively frequent.
View Article and Find Full Text PDF

Download full-text PDF

Source Listing
July 2006