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Tytuł:
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Clinical phenotype of mitochondrial diabetes due to rare mitochondrial DNA mutations.
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Autorzy:
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Decoux-Poullot AG; Service d'endocrinologie, diabétologie et médecine de la reproduction, hôpital de l'Archet 2, université Côte d'Azur, CHU de Nice, Nice, France.
Bannwarth S; Inserm, CNRS, IRCAN, Université Côte d'Azur, CHU de Nice, Nice, France.
Procaccio V; IBS laboratoire de génétique, CHU Angers, Angers, France.
Lebre AS; Inserm U781, Service de génétique, Hôpital Necker-Enfants-Malades, Université Paris-Descartes, Paris, France.
Jardel C; Biochimie métabolique, Centre de génétique moléculaire et chromosomique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Vialettes B; Service d'endocrinologie, diabète, maladies métaboliques, Hôpital de la Conception, CHU de Marseille, 13385 Marseille Cedex 5, France.
Paquis-Flucklinger V; Inserm, CNRS, IRCAN, Université Côte d'Azur, CHU de Nice, Nice, France.
Chevalier N; Service d'endocrinologie, diabétologie et médecine de la reproduction, hôpital de l'Archet 2, université Côte d'Azur, CHU de Nice, Nice, France; Institut national de la santé et de la recherche médicale (Inserm), UMR U1065/UNS, Centre méditerranéen de médecine moléculaire (C3M), équipe 5 « Cellular Basis and Signaling of Tumor Metabolism », Université Côte d'Azur, CHU de Nice, Nice, France. Electronic address: .
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Źródło:
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Annales d'endocrinologie [Ann Endocrinol (Paris)] 2020 Jun; Vol. 81 (2-3), pp. 68-77. Date of Electronic Publication: 2020 Apr 28.
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Typ publikacji:
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Journal Article; Multicenter Study
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Język:
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English
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Imprint Name(s):
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Publication: <1990- >: Paris : Elsevier
Original Publication: Paris, Masson.
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MeSH Terms:
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Mutation*
DNA, Mitochondrial/*genetics
Diabetes Mellitus/*genetics
Mitochondrial Diseases/*genetics
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cohort Studies ; DNA Mutational Analysis ; DNA, Mitochondrial/analysis ; Deafness/epidemiology ; Deafness/genetics ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus/etiology ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/genetics ; Female ; France/epidemiology ; Gene Frequency ; Genetic Association Studies ; Humans ; Infant ; Infant, Newborn ; MERRF Syndrome/epidemiology ; MERRF Syndrome/genetics ; Male ; Middle Aged ; Mitochondrial Diseases/complications ; Mitochondrial Diseases/epidemiology ; Phenotype ; Prospective Studies
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Contributed Indexing:
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Keywords: ADN mitochondrial; Diabetes; Diabète; Diabète mitochondrial; Maladie mitochondriale; Mitochondrial DNA; Mitochondrial diabetes; Mitochondrial disease; Mutation rare; Rare mutation
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Substance Nomenclature:
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0 (DNA, Mitochondrial)
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SCR Disease Name:
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Noninsulin-dependent diabetes mellitus with deafness
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Entry Date(s):
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Date Created: 20200516 Date Completed: 20200908 Latest Revision: 20200908
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Update Code:
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20240105
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DOI:
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10.1016/j.ando.2020.04.007
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PMID:
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32409007
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Objective: While the most frequent mutation responsible for mitochondrial diabetes is the point mutation m.3243 A>G of mitochondrial DNA (mtDNA), few data are available about the role of rare mtDNA mutations in the pathophysiology of diabetes. The main objective of our study was to describe the phenotypic characteristics of patients suffering from diabetes linked to rare mtDNA mutations.
Research Design and Methods: We performed a post-hoc analysis of a prospective multicenter cohort of 743 patients with mitochondrial disorder (previously published by the French Network of Mitochondrial Diseases), associated to a literature review of the PubMed database from 1992 to May 2016. We extracted all reported patients with diabetes and identified rare mtDNA mutations and described their clinical and metabolic phenotypes.
Results: The 50 identified patients (10 from the princeps study; 40 from the review of the literature) showed a heterogeneous metabolic phenotype in terms of age, symptoms prior to diagnosis, treatments, and associated clinical and biological signs. However, neurological symptoms were more frequent in case of rare mtDNA mutations compared to the classical m.3243 A>G mutation (P=0.024). In contrast, deafness (65% vs. 95%, P=3.7E-5), macular pattern dystrophy (20% vs. 86%, P=1.6E-10) and nephropathy (8% vs. 28%, P=0.018) were significantly less frequent than in case of the classical m.3243 A>G mutation.
Conclusion: Although no specific metabolic phenotype could be identified suggesting or eliminating implication of rare mtDNA mutations in diabetes, clinical phenotypes featured more frequent neurological signs.
(Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
