help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on May 26, 2009
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-2680
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
94/8/3025    most recent
Author Manuscript (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow View responses
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints, Permissions and Rights
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by LALOI-MICHELIN, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by LALOI-MICHELIN, M.

Submitted on December 8, 2008
Accepted on May 14, 2009

THE CLINICAL VARIABILITY OF MATERNALLY INHERITED DIABETES AND DEAFNESS (MIDD) IS ASSOCIATED WITH THE DEGREE OF HETEROPLASMY IN BLOOD LEUKOCYTES

M. LALOI-MICHELIN, T. MEAS, C. AMBONVILLE, C. BELLANNÉ-CHANTELOT, S. BEAUFILS, P. MASSIN, B. VIALETTES, H. GIN, J. TIMSIT, B. BAUDUCEAU, L. BERNARD, E. BERTIN, J.-F. BLICKLE, J. CAHEN-VARSAUX, A. CAILLEBA, S. CASANOVA, P. CATHEBRAS, G. CHARPENTIER, P. CHEDIN, T. CREA, B. DELEMER, D. DUBOIS-LAFORGUE, F. DUCHEMIN, P. H. DUCLUZEAU, B. BOUHANICK, L. DUSSELIER, T. GABREAU, A. GRIMALDI, B. GUERCI, V. JACQUIN, E. KALOUSTIAN, E. LARGER, A. LECLEIRE-COLLET, F. LORENZINI, J. LOUIS, J. MAUSSET, A. MURAT, S. NADLER-FLUTEAU, F. OLIVIER, V. PAQUIS-FLUCKLINGER, D. PARIS-BOCKEL, I. RAYNAUD, Y. REZNIK, J. P. RIVELINE, S. SCHNEEBELI, E. SONNET, A. SOLA-GAZAGNES, J. L. THOMAS, B. TRABULSI, M. VIRALLY, P. J. GUILLAUSSEAU*, and GEDIAM, Mitochondrial Diabetes French Study Group

APHP, Department of Medicine B, Lariboisiere Hospital, University Paris 7 Denis-Diderot, 75010 Paris; APHP, Department of Genetics, Pitie-Salpetriere Hospital 75013 Paris; APHP, Service of Ophthalmogy, Lariboisiere Hospital, University Paris 7 Denis-Diderot, 75010 Paris; Department of Endocrinology La Timone Hospital, 13274 Marseille; University Hospital, 33064 Pessac; APHP, Department of Immunology and Diabetology, Cochin hospital, Université René-Descartes, 75014 Paris; Begin Hospital, 94160 Saint-Mandé; General Hospital, 28000 Chartres; Robert Debre Hospital 51100 Reims; Department of Internal Medicine B, University Hospital, 67091 Strasbourg; Department of Endocrinology and Diabetology, General Hospital, 95107 Argenteuil; Department of Diabetology, General Hospital 64109 Bayonne; North Cardiology Center, 93207 Saint-Denis; Department of Endocrinology, University Hospital, 42000 Saint-Etienne; Department of Diabetology, Gilles-de-Corbeil Hospital, 91106 Corbeil; Department of Diabetology, General Hospital, 57126 Thionville; Department of Diabetology and endocrinology, Robert Debré hospital 51092 Reims Cédex; Department of Medicine, General Hospital, 80100 Abbeville; Department of Endocrinology, University Hospital, 49933 Angers; Department of Internal Medicine and Hypertension, Rangueil Hospital T 31059 oulouse; Sainte-Blandine Hospital, 57046 Metz; General Hospital, 89011 Auxerre; APHP, Department of Diabetology, Pitie-Salpetriere Hospital, 75013 Paris; Department of Diabetology, Jeanne-d'Arc Hospital 54201 Dommartin-les-Toul; Department of Diabetology, General Hospital 44600 Saint-Nazaire; Department of Endocrinology, General Hospital, 60324 Compiègne; Department of Diabetology, Hôtel Dieu Hospital, 75004 Paris; Department of Diabetology, Rangueil Hospital 31043 Toulouse; Department of Endocrinology and Diabetology, Dupuytren Hospital 87042 Limoges; Department of Endocrinology and Metabolism Diseases, Hotel-Dieu, 44093 Nantes; Department of Diabetology, Saint-Joseph Hospital, 75014 Paris; Department of Endocrinology, General Hospital 46005 Cahors; Unit of Genetics, L'Archet Hospital 06202 Nice; Medical Center, 37000 Tours; Department of Endocrinology, University Hospital, 14033 Caen; Department of Diabetology, Bretagne Sud Hospital, 56322 Lorient; Department of Endocrinology, La Cavale Blanche University Hospital, 29200 Brest; APHP, Department of Internal Medecine, Henri-Mondor Hospital, 94010 Créteil; Department of Diabetology, Y.Le Foll Hospital, 22027 Saint-Brieuc, France

* To whom correspondence should be addressed. E-mail: pierre-jean.guillausseau{at}lrb.aphp.fr.

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 mtDNA (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mitochondrial DNA 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 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 BMI. 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.
Key words: Maternally inherited diabetes and deafness (MIDD) • Heteroplasmy • mutation 3243 A>G • genotype • phenotype




eLetters:

Read all eLetters

Clinical variability of MIDD and blood m.3243A>G heteroplasmy levels
Robert W. Taylor, et al.
JCEM Online, 23 Jun 2009 [Full text]

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2009 by The Endocrine Society