Long-term Clinical Follow-up of Patients with A3243G Mitochondrial tRNA Mutation : Clinical Phenotype and Natural Course / 대한소아신경학회지

PURPOSE:Mitochondrial disorder is a progressive disease, but there are no specific treatment modalities to prevent the progression. Also, there has been little understanding on the pattern of disease progression nor natural history. The aim of this study was to elucidate the initial clinical phenotypes, patterns of the disease progression, and its natural history of the patients with mitochondrial A3243G mutation. METHODS:Among the patients with biochemically or genetically confirmed mitochondrial disorders, 7 patients with A3243G mutation were included in a 7 year follow-up observation(range: 3-11 years). We classified the patients into two groups by the initial clinical presentations:systemic and neurologic onset. They were clinically evaluated with serial brain MRI and MRS for the evaluation of the disease evolution patterns. RESULTS:The clinical manifestations of mitochondrial A3243G mutation were extremely variable; seizure, headache, dementia, myopathy, sensorineural hearing loss, external ophthalmoplegia, diabetes mellitus, cardiomyopathy, easy fatigability, and short stature. Among the 7 patients, 4 patients initially presented neurologic symptom such as seizure(3) and headache(1), and 3 patients systemic symptoms such as DM(2) and easy fatigability(1). All the patients with neurologic onset showed relentless progression with recurrent stroke- like episodes and intractable seizures, and finally fell into be functionally dependent states or death. All the patients with systemic onset showed clinically silent periods for 3-10 years, and still they were in functionally independent states despite subsequent neurologic symptoms. CONCLUSION:We could find out the relationship between initial clinical phenotypes and final outcomes in mitochondrial A3243G mutation. However, the population is small in this study so that a larger scaled analysis is needed.

The quantitative analysis the number of mitochondrial DNA copy using real-time PCR and mitochondrial tRNA mutation analysis at position 3243 in Korean gestational diabetes mellitus / 대한산부인과학회지

OBJECTIVE: Mitochondrial gene mutations may play a role in the development of gestational diabetes mellitus. This study has assisted to confirm the relationship between the mitochondrial DNA copy number and the GDM. METHODS: Peripheral blood samples were collected from 68 patients with GDM and from 79 controls. For the quantification of mtDNA content, a comparative analysis was performed by the amplification of endogenous control (nuclear DNA, 28S rRNA). The mitochondrial A3243G mutation analysis performed. RESULTS: The ratio of mtDNA/28S rRNA was 1.2053 +/- 0.8307 in GDM patients and 1.7975 +/- 1.1355 in control group (p=0.0004), respectively. Among 68 GDM patients, the mutation in tRNA nt 3243 was detected in only one subject. The A3243G mutation in tRNA- Leu gene, implicated in GDM was reported in 1 of 68 (1.47%) but not in controls. CONCLUSION: In this investigation, blood samples from GDM patients using the real-time polymerase chain reaction will be applied to confirm the relationship between the mitochondrial DNA copy number and the GDM. It is hypothesized that this method will help to predict GDM, and aid in developing early diagnostic methods and treatment modalities.