title: Prevalence and clinical characteristics of maternally inherited diabetes and deafness caused by the mt3243A > G mutation in young adult diabetic subjects in Sri Lanka.
abstract: OBJECTIVE
  The maternally inherited mt3243A > G mutation is associated with a variable clinical phenotype including diabetes and deafness (MIDD). We aimed to determine the prevalence and clinical characteristics of MIDD in a large South Asian cohort of young adult-onset diabetic patients from Sri Lanka.
  
  
  METHODS
  DNA was available from 994 subjects (age of diagnosis 16-40 years, age at recruitment < or = 45 years). Mutation screening was performed using a QRT-PCR method on an ABI 7900HT system using sequence-specific probes. Samples with heteroplasm > or = 5.0% were considered positive.
  
  
  RESULTS
  Nine (four males) mutation-positive subjects were identified (prevalence 0.9%). They were diagnosed at a younger age (25.9 +/- 4.8 years vs. 31.9 +/- 5.6 years, P = 0.002) and were lean (body mass index [BMI] 18.7 +/- 2.7 kg/m(2) vs. 24.7 +/- 4.0 kg/m(2), P < 0.001) compared to NMCs. One mutation-positive subject (11.1%) had metabolic syndrome, compared to 633 (64.3%) of NMCs. Insulin therapy within 6 months of diagnosis was used in four (44.0%) carriers compared to 6.9% of NMCs (P = 0.002). Combined screening criteria of any two of maternal history of diabetes, personal history of hearing impairment and family history of hearing impairment only identified five (55%) of the carriers, with a positive predictive value of 7.4%.
  
  
  CONCLUSIONS
  The prevalence of mt3243A > G mutation among young adult-onset diabetic subjects from Sri Lanka was 0.9%. Our study demonstrates that a maternal family history of diabetes and either a personal and/or family history of deafness only distinguish half of patients with MIDD from Sri Lankan subjects with young-onset diabetes.
authors.affiliation: Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, UK, and Faculty of Medicine, University of Columbo, Sri Lanka.
authors.forename: P
authors.initials: P
authors.lastname: Katulanda
authors.forename: C J
authors.initials: CJ
authors.lastname: Groves
authors.forename: A
authors.initials: A
authors.lastname: Barrett
authors.forename: R
authors.initials: R
authors.lastname: Sheriff
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: A L
authors.initials: AL
authors.lastname: Gloyn
mesh_terms: D000293:Adolescent; D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000150:complications / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D013188:Sri Lanka
chemical_list: D004272:DNA, Mitochondrial