دورية
Increasing knowledge in IGF1Rdefects: lessons from 35 new patients
| العنوان: | Increasing knowledge in IGF1Rdefects: lessons from 35 new patients |
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| المؤلفون: | Giabicani, Eloi¨se, 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-Francois, Storey, Caroline, Thomas, Domitille, Le Bouc, Yves, Rossignol, Sylvie, Netchine, Irène, Brioude, Frédéric |
| المصدر: | Journal of Medical Genetics (JMG); 2020, Vol. 57 Issue: 3 p160-168, 9p |
| مستخلص: | BackgroundThe 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 IGF1Rdefect was described, from which a clinical score was established for diagnosis. We assessed this score in a large cohort of patients with identified IGF1Rdefects, 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.MethodsDNA 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.ResultsWe detected 21 IGF1Rdefects 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.ConclusionWe report eight new pathogenic variants of IGF1Rand an original case with a homozygous SNV. We found the recently proposed clinical score to be accurate for the diagnosis of IGF1Rdefects with a sensitivity of 95.2%. We developed an efficient functional test to assess the pathogenicity of SNVs, which is useful, especially for VUS. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00222593 14686244 |
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| DOI: | 10.1136/jmedgenet-2019-106328 |