title: A novel unstable mutation in mitochondrial DNA responsible for maternally inherited diabetes and deafness.
abstract: OBJECTIVE
  The m.3243A>G mutation in mitochondrial DNA (mtDNA) is responsible for maternally inherited diabetes and deafness (MIDD). Other mtDNA mutations are extremely rare.
  
  
  METHODS
  We studied a patient presenting with diabetes and deafness who does not carry the m.3243A>G mutation.
  
  
  RESULTS
  We identified a deficiency of respiratory chain complex I in the patient's fibroblasts. mtDNA sequencing revealed a novel mutation that corresponds to an insertion of one or two cytosine residues in the coding region of the MT-ND6 gene (m.14535_14536insC or CC), leading to premature stop codons. This heteroplasmic mutation is unstable in the patient's somatic tissues.
  
  
  CONCLUSIONS
  We describe for the first time an unstable mutation in a mitochondrial gene coding for a complex I subunit, which is responsible for the MIDD phenotype. This mutation is likely favored by the m.14530T>C polymorphism, which is homoplasmic and leads to the formation of an 8-bp polyC tract responsible for genetic instability.
authors: Department of Medical Genetics, Archet 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France.
authors: Sylvie
authors: S
authors: Bannwarth
authors: Meriame
authors: M
authors: Abbassi
authors: René
authors: R
authors: Valéro
authors: Konstantina
authors: K
authors: Fragaki
authors: Noémie
authors: N
authors: Dubois
authors: Bernard
authors: B
authors: Vialettes
authors: Véronique
authors: V
authors: Paquis-Flucklinger
mesh_terms: D000368:Aged; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics*; D006801:Humans; D008297:Male; D028361:Mitochondrial Diseases / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I