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.

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.

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

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

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

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

وصف الملف: 1 full-text file(s): application/pdf

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

المؤلفون: Dessein, Anne-Frédérique, Fontaine, Monique, Joncquel-Chevalier Curt, Marie, Briand, Gilbert, Sechter, Claire, Mention-Mulliez, Karine, Dobbelaere, Dries, Douillard, Claire, Lacour, Arnaud, Redonnet-Vernhet, Isabelle, Lamireau, Delphine, Barth, Magalie, Minot-Myhié, Marie-Christine, Kuster, Alice, de Lonlay, Pascale, Gregersen, Niels, Acquaviva, Cécile, Vianey-Saban, Christine, Vamecq, Joseph

المصدر: Dessein , A-F , Fontaine , M , Joncquel-Chevalier Curt , M , Briand , G , Sechter , C , Mention-Mulliez , K , Dobbelaere , D , Douillard , C , Lacour , A , Redonnet-Vernhet , I , Lamireau , D , Barth , M , Minot-Myhié , M-C , Kuster , A , de Lonlay , P , Gregersen , N , Acquaviva , C , Vianey-Saban , C & Vamecq , J 2017 , ' Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate β-oxidation in symptomatic patients with ACADS gene ....

مصطلحات موضوعية: Journal Article

الوصف: BACKGROUND: Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C>T and c.625G>A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid β-oxidation still remains, however, unclear. METHODS: De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16-(2)H3,15-(2)H2-palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted β-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade. Determinations in 301 control subjects of ratios between deuterated butyrylcarnitine and sum of deuterated C2 to C14 acylcarnitines served here as reference values to state specifically functional SCAD impairment in patients addressed for clinical and/or biological suspicion of a β-oxidation disorder. RESULTS: Functional SCAD impairment was found in 39 patients. The 27 patients accepting subsequent gene studies were all positive for ACADS mutations. Twenty-six of 27 patients were positive for c.625G>A variant. Twenty-three of 27 patients harbored susceptibility variants as sole ACADS alterations (18 homozygous and 3 heterozygous for c.625G>A, 2 compound heterozygous for c.625G>A/c.511C>T). CONCLUSION: Our present fluxomic assessment of SCAD suggests a link between ACADS susceptibility variants and abnormal β-oxidation consistent with known altered kinetics of these variants.

العلاقة: https://pure.au.dk/portal/en/publications/2badf1b2-a7aa-4199-9e6a-9cf7ba21e67aTest

الإتاحة: https://doi.org/10.1016/j.cca.2017.05.026Test
https://pure.au.dk/portal/en/publications/2badf1b2-a7aa-4199-9e6a-9cf7ba21e67aTest

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.