Prevalence and clinical characteristics of maternally inherited diabetes and deafness caused by the mt3243A > G mutation in young adult diabetic subjects in Sri Lanka.
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.
Katulanda
P
P
Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, UK, and Faculty of Medicine, University of Columbo, Sri Lanka.
Groves
C J
CJ
Barrett
A
A
Sheriff
R
R
Matthews
D R
DR
McCarthy
M I
MI
Gloyn
A L
AL
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
D004272:DNA, Mitochondrial