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. RESEARCH DESIGN AND 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.
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. RESEARCH DESIGN AND 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.
Authors: Johan L K Van Hove; Cynthia Freehauf; Shelley Miyamoto; Georgirene D Vladutiu; Jacklyn Pancrudo; Eduardo Bonilla; Mark A Lovell; Gary W Mierau; Janet A Thomas; Sara Shanske Journal: Eur J Pediatr Date: 2007-09-22 Impact factor: 3.183
Authors: J Uusimaa; H Jungbluth; C Fratter; G Crisponi; L Feng; M Zeviani; I Hughes; E P Treacy; J Birks; G K Brown; C A Sewry; M McDermott; F Muntoni; J Poulton Journal: J Med Genet Date: 2011-10 Impact factor: 6.318