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, Eloise, Willems, Marjolaine, Steunou, Virginie, Chantot-Bastaraud, Sandra, Thibaud, Nathalie, Abi Habib, Walid, Azzi, Salah, Lam, Bich, Bérard, Laurence, Bony-Trifunovic, Hélène, Brachet, Cécile, Brischoux-Boucher, Elise, Caldagues, Emmanuelle, Coutant, Regis, 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, Sechter, Claire, Souchon, Pierre François, Storey, Caroline, Thomas, Domitille, Le Bouc, Yves, Rossignol, Sylvie, Netchine, Irène, Brioude, Frédéric |
| المصدر: | Journal of medical genetics |
| سنة النشر: | 2019 |
| المجموعة: | DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB) |
| مصطلحات موضوعية: | Biologie, Génétique clinique, fetal growth restriction, homozygous variant, IGF-I, IGF1R, small for gestational age |
| الوصف: | 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. ; SCOPUS: ar.j ; info:eu-repo/semantics/published |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| العلاقة: | uri/info:doi/10.1136/jmedgenet-2019-106328; uri/info:pmid/31586944; uri/info:scp/85073159461; https://dipot.ulb.ac.be/dspace/bitstream/2013/297140/3/IGF1R.pdfTest; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/297140Test |
| الإتاحة: | http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/297140Test https://dipot.ulb.ac.be/dspace/bitstream/2013/297140/3/IGF1R.pdfTest |
| رقم الانضمام: | edsbas.23085ECA |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |