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相關文獻
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頁籤選單縮合
題 名 | Phenotypic Heterogeneity in a Chinese Family with Mitochondrial Disease and A3243G Mutation of Mitochondrial DNA=帶有粒線體DNA之A3243G突變的一個中國人家族之臨床病變異質性 |
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作 者 | 戴道恩; 李新城; 馮清榮; 鄭欽明; 黃秀芬; 魏耀揮; | 書刊名 | 中華醫學雜誌 |
卷 期 | 63:1 2000.01[民89.01] |
頁 次 | 頁71-76 |
分類號 | 415.149 |
關鍵詞 | 異質性; MELAS症候群; 粒線體DNA; 突變; 表現型; Heterogeneity; Heteroplasmy; MELAS syndrome; Mitochondrial DNA; Mutation; Phenotype; |
語 文 | 英文(English) |
中文摘要 | 粒線體 DNA 的 A3243G 點突變已被證實與 MELAS 症候群、糖尿病及某些神經肌 肉疾病有關。 我們自一位 38 歲疑似罹患 MELAS 症候群與糖尿病的男性患者取得了肌肉檢 體, 然後利用聚合�t鏈鎖反應-限制�t片段長度多型性( PCR-RFLP )來分析粒線體 DNA 的 A3243G 點突變,並以電子顯微鏡檢視粒線體的結構變化。我們發現這位患者和其母親所 表現的臨床病徵及粒線體 DNA 之 A3243G 突變的含量很不一樣。 這位患者罹患非典型的 MELAS 症候群、復發血管性頭痛與糖尿病,而其母親則表現慢性進行性外眼肌痲痺症候群與 糖尿病。 這位患者的腦部核磁共振造影於 T2WI 的分析下顯示, 在 temporo-parieto-occipital 區域有由病變引起的高強影像訊號。 他的血中乳酸濃度為 2.32-4.70 mmol/l (正常值 0.67-2.47mmol/l ), 且進食後 2 小時的血糖濃度為 124-148mg/dl。 患者母親的血中乳酸及進食後的血糖濃度分別為 3.15mmol/l 及 192mg/dl 。這位患者的肌肉檢體經電子顯微鏡檢查顯示,粒線體內膜的密度降低且有結構變形,但以 Gomori trichrome 染色卻未發現有糙紅肌絲纖維的存在。 患者和他母親的頭髮毛囊與血球 都有粒線體 DNA 之 tRNA 基因的 A3243G 點突變。 他的頭髮毛囊與血球中的突變型粒線體 DNA 分別佔 36.8% 及 35.2%,而他母親的頭髮毛囊與血球中的突變型粒體 DNA 含量則分別 為 28.8% 及 13.9%。我們認為粒線體 DNA 的 A3243G 點突變在同一家族的不同母系親屬中 , 可分別引起非典型的 MELAS 症候群與糖尿病或慢性進行性眼肌痲痺症候群與糖尿病,而 這種臨床病徵的不同表現, 可能是因為 A3243G 突變型粒線體 DNA 於患者的病變組織中有 不同的隨意分佈所造成。 |
英文摘要 | The A3243G mutation of mitochondrial DNA (mtDNA) has been shown to be responsible for or associated with mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes (MELAS) syndrome, diabetes mellitus (DM) and several other neuromuscular diseases. We used polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) to identify the A3243G mtDNA mutation and an electron microscope to examine mitochondrial derangement in the muscle biopsies of a 38-year-old man suspected to have MELAS syndrome with DM. We found great variability in the clinical presentation and in the proportion of mtDNA with the A3243G mutation in the matrilineal family members of the patient. The proband had atypical MELAS syndrome, recurrent vascular headache, and DM (MELASDM), and his mother manifested chronic progressive ptosis and DM(CPPDM). Brain magnetic resonance imaging of the proband showed high signal intensity in the left temporoparieto-occipital area on T2 weighted images (T2WI). The blood lactate level ranged from 2.32 to 4.70 mmol/l, and two-hour postprandial glucose ranged from 124 mg/dl to 148 mg/dl. The blood lactate and postprandial glucose of the proband's mother were 3.15 mmol/l and 192 mg/dl, respectively. Electron microscopic examination of a muscle biopsy of the patient showed abnormal mitochondria with decreased density of cristae and membrane degeneration. No ragged-red fibers were detected in muscle upon staining with modified Gomori trichrome. The hair follicles and blood cells of the patient and his mother showed the A3243G mutation in the tRNA gene. The proportions of the mutant DNA in the hair follicles and blood cells of the proband were 36.8% and 35.2%, respectively, and those of the patient's mother were 28.8% and 13.9%, respectively. We conclude that the A3243G mtDNA mutation may manifest with MELASDM or CPPDM in different matrilineal members of the same family as a result of differences in random segregation of the heteroplasmic A3243G mutant mtDNA in the affected tissues of patients. |
本系統中英文摘要資訊取自各篇刊載內容。