Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

T. Meas C. Ambonville Christine Bellanné-Chantelot 1 S.. Beaufils Philippe Massin 2 B. Vialettes 3 H. Gin 4, 5 José Timsit 6 B. Bauduceau 7 Louis Bernard 8, 9 E. Bertin 10 J.-F. Blickle J. Cahen-Varsaux A. Cailleba S. Casanova 11 P. Cathebras 12 Guillaume Carpentier 13 P. Chedin T. Crea Brigitte Delemer 14 Danièle Dubois-Laforgue 15, 16, 6, 17, 18 F. Duchemin Pierre-Henri Ducluzeau-Fieloux 19 Béatrice Bouhanick 20 L. Dusselier 21 T. Gabreau A. Grimaldi 22 Bruno Guerci 23 V. Jacquin E. Kaloustian 24 Etienne Larger 25, 17 A. Lecleire-Collet F. Lorenzini J. Louis 26 J. Mausset Arnaud Murat 27 S. Nadler-Fluteau F. Olivier 28 Veronique Paquis-Flucklinger 29, 30 D. Paris-Bockel 31 I. Raynaud Yves Reznik 32, 33 Jean-Pierre Riveline 34, 35 S. Schneebeli E. Sonnet 36 Agnès Sola-Gazagnes J-L Thomas B. Trabulsi M. Virally P. Guillausseau 37 Marie Laloi-Michelin 38
25 Angiogénèse embryonnaire et pathologique
UPMC - Université Pierre et Marie Curie - Paris 6, CIRB - Centre interdisciplinaire de recherche en biologie, INSERM - Institut National de la Santé et de la Recherche Médicale : U833
Abstract :

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue.

Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes.

Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded.

Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender.

Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.

Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness.

Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal.univ-angers.fr/hal-03275645
Contributeur : Okina Université d'Angers <>
Soumis le : jeudi 1 juillet 2021 - 12:27:51
Dernière modification le : mardi 13 juillet 2021 - 03:26:56

Lien texte intégral

Identifiants

Citation

T. Meas, C. Ambonville, Christine Bellanné-Chantelot, S.. Beaufils, Philippe Massin, et al.. The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes. The Journal of clinical endocrinology & metabolism, 2009, 94 (8), pp.3025 - 3030. ⟨10.1210/jc.2008-2680⟩. ⟨hal-03275645⟩

Partager

Métriques

Consultations de la notice

48