Association of clinical features with mitochondrial DNA 3243 A to G mutation heteroplasmy levels in patients with maternally inherited diabetes and deafness

Abstract

Objective To summarize the clinical phenotype profiles and mitochondrial DNA mutation in maternally inherited diabetes and deafness(MIDD), and to improve the diagnosis and treatment of this disease in clinical practice. Methods Sixteen patients with MIDD in six families from Peking Union Medical College from 2007 to Dec 2014 were confirmed as carrying the mitochondrial(mt)DNA 3243 A to G mutation. Sanger sequencing was used to detect the mt DNA 3243 A to G mutation. The peak height G/A ratio was used to determine mutation heteroplasmy levels. Results The patients with early onset of diabetes(35.0±14.6 years), deafness, normal or lower body mass index(BMI), and maternal hereditary tendency suggested the diagnosis of MIDD. The peak height G/A ratio was significantly different according to the onset age of MIDD[≤25 years(61.6±20.17)%; 25-45 years(16.59±8.64)%; >45 years(6.37±0.59)%; P<0.01]. The peak height G/A ratio was negatively correlated with the onset age of MIDD(r=-0.785, P=0.001). Conclusion Early onset of diabetes with deafness, normal/lower BMI, and maternal hereditary tendency strongly suggests the diagnosis of MIDD. The peak height G/A ratio might provide a simple prediction regarding the onset age and severity of MIDD. Key words: Maternally inherited diabetes and deafness; Mitochondrial DNA 3243 heteroplasmy; Clinical features