MITOCHONDRIAL TRNA(LEU(UUR)) GENE MUTATION DIABETES-MELLITUS IN CHINESE

Objective To ascertain the prevalence and clinical features of mitocho ndrial tRNA(leu(UUR)) gene nucleotide (nt) 3243 A-->C mutation diabete s mellitus in Chinese and to establish the approaches preaches for gen etic diagnosis of this subtype oi diabetes during routine daily clinic al practice. Methods Mitochondrial nt 3243 A --> G mutation was screen ed among 207 unrelated non-insulin-dependent diabetes mellitus (NIDDM) patients by using polymerase chain reaction (PCR)/Apa I restriction e ndonuclease digestion. Samples with positive result were confirmed by DNA sequence analysis. Genetic and clinical analysis were carried out in family members of the proband with positive genetic diagnosis. Resu lts Positive results were found in two subjects during screening of un related NIDDM patients, which account for 2.4%-11.1% of NIDDM subjects with uncommon clinical features (with early age-of-onset, with low bo dy-mass-index and on insulin therapy) or with positive family history oi diabetes consistent with or unable re exclude from maternal inherit ance. Genetic diagnosis was positive in 10 out of 25 family members in the pedigrees of these two probands. Conclusions Mitochondrial rRNA(L eu(UUR)) gene nt 3242 A-->G mutation should be considered in diabetic patients with the above-mentioned clinical features. The generic diagn osis in daily clinical practice can be pcriormed with allele specific priming amplification, or PCR/Hae III or Apa I digestion which are tec hnically simple to perform and diagnostically easy to define.