title: A novel mitochondrial DNA missense mutation at G3421A in a family with maternally inherited diabetes and deafness.
abstract: OBJECTIVE
  Mutations in mtDNA are thought to be responsible for the pathogenesis of maternally inherited diabetes. Here, we report a family with maternally inherited diabetes and deafness whose members did not harbour the mtDNA A3243G mutation, the most frequent point mutation in mitochondrial diabetic patients. This study aimed to investigate a possible other mtDNA mutation and its prevalence in type 2 diabetic patients.
  
  
  METHODS
  Height, body weight, waistline, and hip circumference were measured and serum biochemical marks determined in all members of the family. In addition, a 75 g oral glucose tolerance test and electric listening test were conducted in these members. Genomic DNA was prepared from peripheral leukocytes. Direct sequencing of PCR products was used to detect the mtDNA mutation in this family. The prevalence of mtDNA G3421A nucleotide substitutions was investigated by restriction fragment length polymorphism analysis in 1350 unrelated type 2 diabetic patients recruited by random cluster sampling from the central city area of Shanghai, China.
  
  
  RESULTS
  (1) A new missense homoplasmic mutation of mtDNA G3421A was found in a maternally inherited diabetic family and existed neither in 1350 unrelated type 2 diabetic patients nor in 50 non-diabetic individuals. (2) The mode of mutation and diabetes transmission was typical maternal inheritance in this family. (3) All diabetic family members were found to have an onset at 35-42 years of age, accompanied by deafness of varying degrees.
  
  
  CONCLUSIONS
  mtDNA G3421A (Val39Ile) found in a family with maternally inherited diabetes and deafness is a novel missense mutation. Whether this is a diabetogenic mutation and its effect on mitochondrial function needs to be further studied.
authors.affiliation: Department of Endocrinology, Institute of Endocrinology and Diabetology, Huashan Hospital, Fu Dan University, 12 Middle Wurumqi Road, Shanghai 200040, People's Republic of China.
authors.forename: F L
authors.initials: FL
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: X Y
authors.initials: XY
authors.lastname: Song
authors.forename: H Y
authors.initials: HY
authors.lastname: Hu
authors.forename: H B
authors.initials: HB
authors.lastname: Xu
authors.forename: X M
authors.initials: XM
authors.lastname: Zhang
authors.forename: J H
authors.initials: JH
authors.lastname: Shi
authors.forename: J
authors.initials: J
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: B
authors.initials: B
authors.lastname: Lu
authors.forename: X C
authors.initials: XC
authors.lastname: Wang
authors.forename: R M
authors.initials: RM
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial