دورية أكاديمية
Increasing knowledge in IGF1R defects: lessons from 35 new patients
| العنوان: | Increasing knowledge in IGF1R defects: lessons from 35 new patients |
|---|---|
| المؤلفون: | Giabicani, Eloïse, Willems, Marjolaine, Steunou, Virginie, Chantot-Bastaraud, Sandra, Thibaud, Nathalie, Habib, Walid, Abi, Azzi, Salah, Lam, Bich, Bérard, Laurence, Bony-Trifunovic, Hélène, Brachet, Cécile, Brischoux-Boucher, Elise, Caldagues, Emmanuelle, Coutant, Régis, Cuvelier, Marie-Laure, Gelwane, Georges, Guemas, Isabelle, Houang, Muriel, Isidor, Bertrand, Jeandel, Claire, Lespinasse, James, Naud-Saudreau, Catherine, Jesuran-Perelroizen, Monique, Perrin, Laurence, Piard, Juliette, C, Sechter, Claire, Souchon, Pierre-François, Storey, Caroline, Thomas, Domitille, Le Bouc, Yves, Rossignol, Sylvie, Netchine, Irène, Brioude, Frédéric |
| المساهمون: | Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, Children's University Hospital Queen Fabiola Bruxelles, Belgium, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté COMUE (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier de Calais, Hôpital Robert Debré Paris, Hôpital Robert Debré, Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Métropole Savoie Chambéry, CH Bretagne Sud, Association Française des Pédiatres Endocrinologues Libéraux (AFPEL), Hôpital universitaire Robert Debré Reims (CHU Reims), AP-HP Hôpital universitaire Robert-Debré Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| المصدر: | ISSN: 0022-2593. |
| بيانات النشر: | HAL CCSD BMJ Publishing Group |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | homozygous variant, small for gestational age, IGF-I, fetal growth restriction, IGF1R, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics |
| الوصف: | International audience ; 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 IGF1R defect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1R 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 IGF1R 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 IGF1R. Functional studies showed that the SNVs tested were associated with decreased AKT phosphorylation.CONCLUSION: We report eight new pathogenic variants of IGF1R and an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1R 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31586944; hal-02435128; https://hal.sorbonne-universite.fr/hal-02435128Test; https://hal.sorbonne-universite.fr/hal-02435128/documentTest; https://hal.sorbonne-universite.fr/hal-02435128/file/Giabicani%20et%20al.%20-%202019%20-%20Increasing%20knowledge%20in%20IGF1R%20defects%20lessons%20fro.pdfTest; PUBMED: 31586944; WOS: 000518193900003 |
| DOI: | 10.1136/jmedgenet-2019-106328 |
| الإتاحة: | https://doi.org/10.1136/jmedgenet-2019-106328Test https://hal.sorbonne-universite.fr/hal-02435128Test https://hal.sorbonne-universite.fr/hal-02435128/documentTest https://hal.sorbonne-universite.fr/hal-02435128/file/Giabicani%20et%20al.%20-%202019%20-%20Increasing%20knowledge%20in%20IGF1R%20defects%20lessons%20fro.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.AEBDB942 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/jmedgenet-2019-106328 |
|---|