Phenotypic expression of diabetes secondary to a T14709C mutation of mitochondrial DNA. Comparison with MIDD syndrome (A3243G mutation): a case report.
OBJECTIVE
To analyze the clinical and biochemical features of a recently described point mutation of mitochondrial DNA associated with diabetes. This mutation, characterized by a T14709C transition of a highly conserved nucleotide in the region coding for the glutamic acid tRNA, is heteroplasmic.


METHODS
The phenotypic expression in the insulin-requiring diabetic proband from the pedigree was compared to that of diabetic probands from three families with the classic A3243G mtDNA mutation (maternally inherited diabetes and deafness [MIDD] syndrome). The same investigations to evaluate pancreatic neurosensorial and muscle involvement were performed in all four patients.


RESULTS
The natural courses of the diabetes and the hearing defects were not different between the two mutations. The patient with the 14,709 mutation, however, exhibited a milder alteration of pigmentary epithelium of retina and a much more severe muscle involvement, as attested by the clinical expression and the concurrent anomalies of muscle energy production evidenced by 31P magnetic resonance spectroscopy, confirming the profound impairment of oxidative processes.


CONCLUSIONS
This novel mutation has to be added to the other known mtDNA anomalies in order to ascribe some diabetes suspected to arise from mitochondrial defects to this nosological framework.
Vialettes
B H
BH
Laboratoire de Neurobiologie Cellulaire, Faculté de Médecine, Centre National de la Recherche Scientifique (CNRS) Unite Mixte de Recherche (UMR) 6549, France.
Paquis-Flucklinger
V
V
Pelissier
J F
JF
Bendahan
D
D
Narbonne
H
H
Silvestre-Aillaud
P
P
Montfort
M F
MF
Righini-Chossegros
M
M
Pouget
J
J
Cozzone
P J
PJ
Desnuelle
C
C
D000328:Adult; D000792:Angiography / Q000379:methods; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005654:Fundus Oculi; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012352:RNA, Transfer, Glu / Q000235:genetics*; D013577:Syndrome
D017931:DNA Primers; D004272:DNA, Mitochondrial; D012352:RNA, Transfer, Glu