المؤلفون: Humbert, Linda, Proust-Lemoine, Emmanuelle, Dubucquoi, Sylvain, Kemp, Elisabeth Helen, Saugier-Veber, Pascale, Fabien, Nicole, Raymond-Top, Isabelle, Cardot-Bauters, Catherine, Carel, Jean-Claude, Cartigny, Maryse, Chabre, Olivier, Chanson, Philippe, Delemer, Brigitte, Do Cao, Christine, Guignat, Laurence, Kahn, Jean-Emmannuel, Kerlan, Veronique, Lefebvre, Herve, Linglart, Agnes, Mallone, Roberto, Reynaud, Rachel, Sendid, Boualem, Souchon, Pierre-François, Touraine, Philippe, Wémeau, Jean-Louis, Vantyghem, Marie-Christine

المساهمون: Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), University of Sheffield Sheffield, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hospices Civils de Lyon (HCL), UFR Médecine Santé - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Centre Hospitalier Universitaire CHU Grenoble (CHUGA), Université Paris-Saclay, Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital universitaire Robert-Debré Paris, Hôpital Claude Huriez Lille, Hôpital Cochin AP-HP, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital de la Timone CHU - APHM (TIMONE), Aix Marseille Université (AMU), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital universitaire Robert Debré Reims (CHU Reims), Sorbonne Université (SU), Recherche translationnelle sur le diabète - U 1190 (RTD)

المصدر: ISSN: 1945-7197 ; The Journal of clinical endocrinology & metabolism ; https://hal.univ-lille.fr/hal-04633764Test ; The Journal of clinical endocrinology & metabolism, 2024, J Clin Endocrinol Metab, ⟨10.1210/clinem/dgae211⟩.

مصطلحات موضوعية: APECED syndrome, autoimmune polyendocrine syndrome type 1, AIRE genotype, asplenia, pulmonary involvement, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome is a rare disease caused by biallelic mutations of the AIRE gene, usually presenting with the triad hypoparathyroidism-adrenal failure-chronic mucocutaneous candidiasis (CMC) and nonendocrine manifestations. The aim of this study was to determine the molecular profile of the AIRE gene, the prevalence of rare manifestations, and to characterize immunological disturbances in a French cohort.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38605470; hal-04633764; https://hal.univ-lille.fr/hal-04633764Test; https://hal.univ-lille.fr/hal-04633764/documentTest; https://hal.univ-lille.fr/hal-04633764/file/dgae211.pdfTest; PUBMED: 38605470

الإتاحة: https://doi.org/10.1210/clinem/dgae211Test
https://hal.univ-lille.fr/hal-04633764Test
https://hal.univ-lille.fr/hal-04633764/documentTest
https://hal.univ-lille.fr/hal-04633764/file/dgae211.pdfTest

المؤلفون: Le Collen, Lauriane, Barraud, Sara, Braconnier, Antoine, Coppin, Lucie, Zachar, Dominique, Boulagnon, Camille, Deguelte, Sophie, Souchon, Pierre Francois, Spodenkiewicz, Marta, Poirsier, Celine, Aubert, Sebastien, Odou, Marie-Francoise, Delemer, Brigitte

المساهمون: CNRS, Université de Lille, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199, Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 CRESTIC, Hôpital universitaire Robert Debré Reims, Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277, Université de Reims Champagne-Ardenne URCA, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

مصطلحات موضوعية: Knudson two-hit hypothesis, Large rearrangements, CDC73, Hyperparathyroidism, Jaw Tumors, HRPT2

الوصف: OBJECTIVE: We described the phenotype of a large 4-generation family with Hyperparathyrodism-Jaw Tumor syndrome (HPT-JT) associated with a rare deletion of exon 3 of the CDC73 gene. METHODS: We collected medical, genetic data on 24 family members descended from a common ancestor carrying a heterozygous deletion of exon 3. RESULTS: Thirteen carried the deletion, the penetrance was estimated at 50% at 40 years. Seven patients (39 ± 14.5 years) presented with HPT which could start at 13. Median plasmatic calcium and PTH levels were 3.13 ± 0.7 mmol/L and 115 ± 406 pg/ml, respectively. Kidney disease related to hypercalcemia were present in 57.1% of patients. All seven patients underwent surgery to remove a single parathyroid adenoma. One recurrence occurred 7 years post-surgery. No parathyroid carcinoma has been found to date. We found two atypical parathyroid adenomas. We described an additional somatic variant in exon 1 of gene CDC73 in two tumors. Jaw tumors were not necessarily associated with hyperparathyroidism, as shown in one case. Two kidney cysts were also reported. Variable phenotype expressivity was emphasized by clinical presentations in 2 monozygotic twins: acute hypercalcemia, kidney failure and ossifying fibroma in one twin, versus normocalcemic parathyroid adenoma in the other one. CONCLUSIONS: We report a family carrier of a deletion of exon 3 of the CDC73 gene. This is characterized by a high level of hypercalcemia, deleterious kidney effects and atypical parathyroid adenomas without carcinomas. Onset and intensity of HPT remain unpredictable. The additional somatic mutation found in the parathyroid tumor could lead to these phenotypical variations. ; 73

العلاقة: Endocrine; http://hdl.handle.net/20.500.12210/40876Test

الإتاحة: https://doi.org/20.500.12210/40876Test
https://hdl.handle.net/20.500.12210/40876Test

المؤلفون: Le Collen, Lauriane, Delemer, Brigitte, Spodenkiewicz, Marta, Cornillet Lefebvre, Pascale, Durand, Emmanuelle, Vaillant, Emmanuel, Badreddine, Alaa, Derhourhi, Mehdi, Mouhoub, Tarik Ait, Jouret, Guillaume, Juttet, Pauline, Souchon, Pierre François, Vaxillaire, Martine, Froguel, Philippe, Bonnefond, Amélie, Doco Fenzy, Martine

المصدر: Orphanet Journal of Rare Diseases ; volume 17, issue 1 ; ISSN 1750-1172

مصطلحات موضوعية: Pharmacology (medical), Genetics (clinical), General Medicine

الوصف: Background We studied a young woman with atypical diabetes associated with mild intellectual disability, lymphedema distichiasis syndrome (LDS) and polymalformative syndrome including distichiasis. We used different genetic tools to identify causative pathogenic mutations and/or copy number variations. Results Although proband’s, diabetes mellitus occurred during childhood, type 1 diabetes was unlikely due to the absence of detectable autoimmunity. DNA microarray analysis first identified a de novo, heterozygous deletion at the chr16q24.2 locus. Previously, thirty-three pathogenic or likely pathogenic deletions encompassing this locus have been reported in patients presenting with intellectual deficiency, obesity and/or lymphedema but not with diabetes. Of note, the deletion encompassed two topological association domains, whose one included FOXC2 that is known to be linked with LDS. Via whole-exome sequencing, we found a heterozygous, likely pathogenic variant in WFS1 (encoding wolframin endoplasmic reticulum [ER] transmembrane glycoprotein) which was inherited from her father who also had diabetes. WFS1 is known to be involved in monogenic diabetes. We also found a likely pathogenic variant in USP9X (encoding ubiquitin specific peptidase 9 X-linked) that is involved in X-linked intellectual disability, which was inherited from her mother who had dyscalculia and dyspraxia. Conclusions Our comprehensive genetic analysis suggested that the peculiar phenotypes of our patient were possibly due to the combination of multiple genetic causes including chr16q24.2 deletion, and two likely pathogenic variants in WFS1 and USP9X .

الإتاحة: https://doi.org/10.1186/s13023-022-02248-2Test

المؤلفون: Berot, Aurélie, Gitton, Anne, Diallo, Alpha Mamadou, Rahim, Assia, Lukas, Céline, Souchon, Pierre François, Salmon, Anne Sophie, François, Maud, Ly, Sang, Vitellius, Géraldine, Decoudier, Bénédicte, Sulmont, Véronique, Delemer, Brigitte, Barraud, Sara

المصدر: Diabetes & Metabolism ; volume 48, issue 5, page 101346 ; ISSN 1262-3636

مصطلحات موضوعية: Endocrinology, General Medicine, Endocrinology, Diabetes and Metabolism, Internal Medicine

الإتاحة: https://doi.org/10.1016/j.diabet.2022.101346Test
https://api.elsevier.com/content/article/PII:S1262363622000295?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1262363622000295?httpAccept=text/plainTest

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: Prigge, Regina, McKnight, John A, Wild, Sarah H, Haynes, Aveni, Jones, Timothy W, Davis, Elizabeth A, Rami-Merhar, Birgit, Fritsch, Maria, Prchla, Christine, Lavens, Astrid, Doggen, Kris, Chao, Suchsia, Aronson, Ronnie, Brown, Ruth, Ibfelt, Else H, Svensson, Jannet, Young, Robert, Warner, Justin T, Robinson, Holy, Laatikainen, Tiina, Rautiainen, Päivi, Delemer, Brigitte, Souchon, Pierre François, Diallo, Alpha M, Holl, Reinhard W, Schmid, Sebastian M, Raile, Klemens, Tigas, Stelios, Bargiota, Alexandra, Zografou, Ioanna, Luk, Andrea O Y, Chan, Juliana C N, Dinneen, Sean F, Buckley, Claire M, Kgosidialwa, Oratile, Cherubini, Valentino, Gesuita, Rosaria, Strele, Ieva, Pildava, Santa, Veeze, Henk, Aanstoot, Henk-Jan, Mul, Dick, Jefferies, Craig, Cooper, John G, Løvaas, Karianne Fjeld, Battelino, Tadej, Dovc, Klemen, Bratina, Nataša, Eeg-Olofsson, Katarina, Svensson, Ann-Marie, Gudbjornsdottir, Soffia, Globa, Evgenia, Zelinska, Nataliya

المساهمون: Prigge, Regina, Mcknight, John A, Wild, Sarah H, Haynes, Aveni, Jones, Timothy W, Davis, Elizabeth A, Rami-Merhar, Birgit, Fritsch, Maria, Prchla, Christine, Lavens, Astrid, Doggen, Kri, Chao, Suchsia, Aronson, Ronnie, Brown, Ruth, Ibfelt, Else H, Svensson, Jannet, Young, Robert, Warner, Justin T, Robinson, Holy, Laatikainen, Tiina, Rautiainen, Päivi, Delemer, Brigitte, Souchon, Pierre Françoi, Diallo, Alpha M, Holl, Reinhard W, Schmid, Sebastian M, Raile, Klemen, Tigas, Stelio, Bargiota, Alexandra, Zografou, Ioanna, Luk, Andrea O Y, Chan, Juliana C N, Dinneen, Sean F, Buckley, Claire M, Kgosidialwa, Oratile, Cherubini, Valentino, Gesuita, Rosaria, Strele, Ieva, Pildava, Santa, Veeze, Henk, Aanstoot, Henk-Jan, Mul, Dick, Jefferies, Craig, Cooper, John G, Løvaas, Karianne Fjeld, Battelino, Tadej, Dovc, Klemen, Bratina, Nataša, Eeg-Olofsson, Katarina, Svensson, Ann-Marie, Gudbjornsdottir, Soffia, Globa, Evgenia, Zelinska, Nataliya

مصطلحات موضوعية: HbA1c, glycaemic control, registers of people with diabete, type 1 diabete, Adult, Blood Glucose, Child, Cross-Sectional Studie, Female, Glycated Hemoglobin A, Glycemic Control, Human, Male, Diabetes Mellitus, Type 1

الوصف: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34890078; info:eu-repo/semantics/altIdentifier/wos/WOS:000734358300001; volume:39; issue:5; journal:DIABETIC MEDICINE; https://hdl.handle.net/11566/307608Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85128493437

الإتاحة: https://doi.org/10.1111/dme.14766Test
https://hdl.handle.net/11566/307608Test

المؤلفون: Roucher-Boulez, Florence, Mallet-Moták, Delphine, Samara-Boustani, Dinane, Jilani, Houweyda, Ladjouze, Asmahane, Souchon, Pierre François, Simon, Dominique, Nivot, Sylvie, Heinrichs, Claudine, Ronze, Maryline, Bertagna, Xavier, Groisne, Laure, Leheup, Bruno, Naud-Saudreau, Naud-Saudreau, Blondin, Gilles, Lefevre, Christine, Lemarchand, Laetitia, Morel, Yves

المساهمون: CHU Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Bab-el-Oued, Centre Hospitalier Universitaire de Bab-el-Oued, Alger, Algérie., American Memorial Hospital (Reims), Service d'Endocrinologie et Diabétologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, CHU Pontchaillou Rennes, Hôpital Universitaire des Enfants Reine Fabiola, Université libre de Bruxelles (ULB), Université médicale de Vienne, Autriche, Centre hospitalier Lucien Hussel, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique Médicale CHRU Nancy, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CH de Lorient, Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire Lille (CHRU Lille), Service de pédiatrie, Hopital Saint-Louis, La Rochelle, Service de pédiatrie, Hopital Saint-Louis , La Rochelle

المصدر: ISSN: 0804-4643.

مصطلحات موضوعية: primary adrenal insufficiency, oxidative stress, nicotinamide nucleotide transhydrogenase, follow-up, massive parallel sequencing, [SDV]Life Sciences [q-bio], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism

الوصف: International audience ; OBJECTIVE: NNT (nicotinamide nucleotide transhydrogenase), one of several genes recently discovered in familial glucocorticoid deficiencies (FGD), is involved in reactive oxygen species detoxification, suggesting that extra-adrenal manifestations may occur, due to the sensitivity to oxidative stress of other organs rich in mitochondria. Here, we sought to identify NNT mutations in a large cohort of patients with primary congenital adrenal insufficiency without molecular etiology and evaluate the degree of adrenal insufficiency and onset of extra-adrenal damages. METHODS: Sanger or massive parallel sequencing of NNT and patient monitoring. RESULTS: Homozygous or compound heterozygous NNT mutations occurred frequently (26%, 13 unrelated families, 18 patients) in our cohort. Seven new mutations were identified: p.Met337Val, p.Ala863Glu, c.3G\textgreaterA (p.Met1?), p.Arg129*, p.Arg379*, p.Val665Profs*29, and p.Ala704Serfs*19. The most frequent mutation, p.Arg129*, was found recurrently in patients from Algeria. Most patients were diagnosed belatedly (8-18 months) after presenting severe hypoglycemia; others experiencing stress conditions were diagnosed earlier. Five patients also had mineralocorticoid deficiency at onset. One patient had congenital hypothyroidism and two cryptorchidism. In follow-up, we noticed gonadotropic and genitalia impairments (precocious puberty, testicular inclusions, interstitial Leydig cell adenoma, azoospermia), hypothyroidism and one hypertrophic cardiomyopathy. Intrafamilial phenotype heterogeneity was observed. CONCLUSIONS: NNT should be sequenced, not only in FGD, but also in all primary adrenal insufficiencies for which the most frequent etiologies have been ruled out. As NNT is involved in oxidative stress, careful follow-up is needed to evaluate mineralocorticoid biosynthesis extent, and gonadal, heart and thyroid function.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/27129361; hal-01321410; https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321410Test; https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321410/documentTest; https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321410/file/NNT%20mutations_accepted.pdfTest; PUBMED: 27129361

الإتاحة: https://doi.org/10.1530/EJE-16-0056Test
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321410Test
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321410/documentTest
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01321410/file/NNT%20mutations_accepted.pdfTest

المؤلفون: Le Collen, Lauriane, Barraud, Sara, Braconnier, Antoine, Coppin, Lucie, Zachar, Dominique, Boulagnon, Camille, Deguelte, Sophie, Souchon, Pierre François, Spodenkiewicz, Marta, Poirsier, Céline, Aubert, Sébastien, Odou, Marie Françoise, Delemer, Brigitte

المساهمون: Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille)

المصدر: ISSN: 0969-711X ; Endocrine ; https://hal.science/hal-03277372Test ; Endocrine, 2021, 73, pp.693-701. ⟨10.1007/s12020-021-02756-4⟩.

مصطلحات موضوعية: [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology

الوصف: International audience

العلاقة: hal-03277372; https://hal.science/hal-03277372Test

الإتاحة: https://doi.org/10.1007/s12020-021-02756-4Test
https://hal.science/hal-03277372Test

المؤلفون: Prigge, Regina, McKnight, John A., Wild, Sarah H., Haynes, Aveni, Jones, Timothy W., Davis, Elizabeth A., Rami‐Merhar, Birgit, Fritsch, Maria, Prchla, Christine, Lavens, Astrid, Doggen, Kris, Chao, Suchsia, Aronson, Ronnie, Brown, Ruth, Ibfelt, Else H., Svensson, Jannet, Young, Robert, Warner, Justin T., Robinson, Holy, Laatikainen, Tiina, Rautiainen, Päivi, Delemer, Brigitte, Souchon, Pierre François, Diallo, Alpha M., Holl, Reinhard W., Schmid, Sebastian M., Raile, Klemens, Tigas, Stelios, Bargiota, Alexandra, Zografou, Ioanna, Luk, Andrea O. Y., Chan, Juliana C. N., Dinneen, Sean F., Buckley, Claire M., Kgosidialwa, Oratile, Cherubini, Valentino, Gesuita, Rosaria, Strele, Ieva, Pildava, Santa, Veeze, Henk, Aanstoot, Henk‐Jan, Mul, Dick, Jefferies, Craig, Cooper, John G., Løvaas, Karianne Fjeld, Battelino, Tadej, Dovc, Klemen, Bratina, Nataša, Eeg‐Olofsson, Katarina, Svensson, Ann‐Marie

المصدر: Diabetic Medicine ; volume 39, issue 5 ; ISSN 0742-3071 1464-5491

الوصف: Aims To update and extend a previous cross‐sectional international comparison of glycaemic control in people with type 1 diabetes. Methods Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic‐based data sources in countries or regions between 2016 and 2020. Median HbA 1c (IQR) and proportions of individuals with HbA 1c < 58 mmol/mol (<7.5%), 58–74 mmol/mol (7.5–8.9%) and ≥75 mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15–24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA 1c < 58 mmol/mol (<7.5%) relative to ≥58 mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA 1c category compared to previous estimates were calculated. Results Median HbA 1c varied from 55 to 79 mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA 1c < 58 mmol/mol (<7.5%) were 0.91 (0.90–0.92) for women compared to men, 1.68 (1.65–1.71) for people aged <15 years and 0.81 (0.79–0.82) aged15–24 years compared to those aged ≥25 years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA 1c < 58 mmol/l (<7.5%) increased and proportions of people with HbA 1c ≥ 75 mmol/mol (≥9.0%) decreased. Conclusions Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub‐optimal for most people with Type 1 diabetes.

الإتاحة: https://doi.org/10.1111/dme.14766Test