- 作者: Rong-Hong Hsieh Jei-Yuan Li Cheng-Yoong Pang Yau-Huei Wei
- 作者服務機構: Department of Biochemistry and Center for Cellular and Molecular Biology, School of Life Science, National Yang-Ming University, Department of Medicine, Taipei Medical Universlty and Department of Obstetrics Kaohsiung veterans General Hospita, Kaohsiung, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Using RNase protection analysis, we found a novel C toG mutation at nucleotide position 3093 of mitochondrialDNA (mtDNA) in a previously reported 35-year-old wom-an exhibiting clinical features of mitochondrial myopa-thy, encephalopathy, lactic acidosis and stroke-like epi-sodes (MELAS) syndrome together with diabetes melli-tus, hyperthyroidism and cardiomyopathy. The patientalso had an A3243G mutation in the tRNA geneand a 260-base pair duplication in the D-loop of mtDNA.The fibroblasts of the patient were cultured and used forthe construction of cybrids using cytoplasmic transfer ofthe patient's mtDNA to the mtDNA-less p cells. RNA iso-lated from the cybrids was subjected to RNase protectionanalysis, and a C3093G transversion at the 16S rRNAgene and a MELAS-associated A3243G mutation ofmtDNA were detected. The novel C3093G mutation to-gether with the A3243G transition were found in musclebiopsies, hair follicles and blood cells of this patient andalso in her skin fibroblasts and cybrids.The proportion ofthe C3093G mutant mtDNA in muscle biopsies of thepatient was 51%. In contrast, the mutation was notdetected in three sons of the proband. To characterizethe impact of the mtDNA mutation-associated defects onmitochondrial function, we determined the respiratoryenzyme activities of the primary culture of fibroblastsestablished from the proband, her mother and her threesons. The proportions of mtDNA with the C3093G trans-version and the A3243G transition in the fibroblasts ofthe proband were 45 and 58%, respectively. However,the fibroblasts of the proband's mother and children har-bored lower levels of mtDNA with the A3243G mutationbut did not contain the C3093G mutation. The complex Iactivity in the proband's fibroblasts was decreased to47% of the control but those of the fibroblasts of themother and three sons of the proband were not signifi-cantly changed. These findings suggest that the C3093Gtransversion together with the A3243G transition ofmtDNA impaired the respiratory function of mitochon-dria and caused the atypical MELAS syndrome associat-ed with diabetes mellitus, hyperthyroidism and cardio-myopathy in this patient.
- 中文關鍵字: --
- 英文關鍵字: MELAS. Mitochondrial DNA. 16S rRNA. RNase protection. Cybrid