摘要
为了检测中国ＭＥＬＡＳ患者的致病因素，采用Ｓｏｕｔｈｅｒｎ印迹杂交、ＰＣＲ、亚克隆及ＤＮＡ测序等技术，对１例中国线粒体脑肌病、乳酸中毒、中风样发作综合征（ｍｉｔｏｃｈｏｎｄｒｉａｌｅｎｃｅｐｈａｌｏｍｙｏｐａｔｈｙｗｉｔｈｌａｃｔｉｃａｃｉｄｏｓｉｓａｎｄｓｔｒｏｋｅ－ｌｉｋｅｅｐｉｓｏｄｅｓ，ＭＥＬＡＳ）患者的线粒体ＤＮＡ（ｍｔＤＮＡ）进行了突变分析。检测到ＭＥＬＡＳ患者特有的Ａ→Ｇ３２４３碱基替换，这一替换导致了一个新的ＡｐａⅠ酶切位点的形成。此突变型ｍｔＤＮＡ在检测的骨骼肌及血液标本中均被发现。突变型ｍｔＤＮＡ在检测的骨骼肌及血液ｍｔＤＮＡ标本中所占的比例分别为８０％和６０％。推测这一影响到ｍｔＤＮＡ中ｔＲＮＡｌｅｕ（ＵＵＲ）基因二氢尿嘧啶环的核苷酸突变是此例ＭＥＬＡＳ的重要致病因素。此外，在所测ｍｔＤＮＡ５６１ｂｐ（２９５０～３５１０）范围内还发现了１个Ｇ→ＴＮＤ１３４２３中性突变。
Applying Southern blot, PCR, subcloning and sequencing techniques, we have analyzed the mtDNA mutation in a Chinese patient with mitochodrial myopathy, encephalopathy, lactic acidosis and stroke like episodes(MELAS). An A→G 3243 substitution was specifically identified in the mtDNA of the MELAs patient. This substitution results in production of a new endonuclease ApaⅠ site. The mutated mtDNA makes up 80 percent and 60 percent of the total mtDNA in skeletal muscle and peripheral blood samples detected respectively. This mutation, which affects a nucleotide position in the dihydrouridine loop of the tRNA leu(UUR) mtDNA gene, was considered the cause of the disease. Additionally, one neutral mutation, G→T ND1 3423 was detected in the mtDNAs with and without the A→G 3243 mutation in the patient.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
1997年第2期73-75,共3页
Chinese Journal of Medical Genetics
基金
国家863资助项目
关键词
线粒体
DNA突变
脑肌病
乳酸中毒
mtDNA Point mutation Mitochondrial encephalomyopathy
