MITOCHONDRIAL DISORDER ASSOCIATED WITH NEWBORN CARDIOPULMONARY ARREST
MITOCHONDRIAL DISORDER ASSOCIATED WITH NEWBORN CARDIOPULMONARY ARREST
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DOI：
10.1203/00006450-199305000-00002
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发表时间：
1993-05-01
影响因子：
3.6
通讯作者：
APRILLE, JR
中科院分区：
文献类型：
--
作者：
YOON, KL;ERNST, SG;APRILLE, JR
研究对象是一名出生后 2.5 天死于低血糖、乳酸性酸中毒和突发多系统衰竭的女婴。生化研究表明，肝脏、肾脏和肌肉中存在复合物 III 和 IV 缺乏，其中肌肉受影响最严重。对患者线粒体 DNA 的 Southern 印迹分析未发现任何缺失。变性梯度凝胶分析通过解链行为的差异来检测单碱基的变化，结果显示出一条额外的条带，而这条条带在母亲、母亲的同卵双胞胎姐妹或无关的正常受试者的线粒体DNA中未见。该额外条带表明含有脱辅细胞色素 b 和转移 RNA(thr) 基因的限制性片段存在异质性。测序显示核苷酸 15923 处存在 A 到 G 的突变，该突变是转移 RNA(thr) 基因反密码子环的最后一个碱基。该突变通过添加配对来延长反密码子茎，并将反密码子环大小从 7 个核苷酸减少到 5 个核苷酸，可能会损害翻译和/或处理多顺反子 RNA 转录物中的转移 RNA(thr) 功能。患者母亲此前生过一名男婴，该男婴也在产后1.5天死亡，且母亲和双胞胎均曾多次流产。在最近一次怀孕期间，对母亲的双胞胎姐妹进行了羊膜穿刺术以进行基因筛查；一些培养的细胞可用于本研究。在出生时获得的羊水细胞或脐带血中未发现该突变；婴儿出生时一切正常，目前仍保持健康。结论是15923位核苷酸的突变很可能是指示病例致命疾病的原因。发病时间与产后糖原储备耗尽一致。研究结果表明，对于在出生后几天内突然发生心肺骤停的婴儿，应考虑线粒体疾病。
A female infant who died 2.5 d after birth with hypoglycemia, lactic acidosis, and sudden multisystem failure was studied. Biochemical studies showed complex III and IV deficiency in liver, kidney, and muscle, with muscle most severely affected. Southern blot analysis of the patient's mitochondrial DNA did not reveal any deletions. Denaturing gradient gel analysis, which detects single base changes by differences in melting behavior, showed an extra band that was not seen in mitochondrial DNA from the mother, the mother's identical twin sister, or an unrelated normal subject. This extra band indicated heteroplasmy for a restriction fragment containing the apocytochrome b and transfer RNA(thr) genes. Sequencing revealed an A to G mutation at nucleotide 15923, the last base of the anticodon loop of the transfer RNA(thr) gene. The mutation lengthens the anticodon stem by added pairing and reduces the anticodon loop size from 7 to 5 nucleotides, potentially compromising transfer RNA(thr) function in translation and/or in processing the polycistronic RNA transcript. The patient's mother previously had a male infant who also died at 1.5 d postnatal, and both the mother and her twin have had multiple miscarriages. Amniocentesis for a genetic screen was performed on the mother's twin sister during a recent pregnancy; some of the cultured cells were made available for this study. The mutation was not found in the amniocytes or in umbilical cord blood obtained at birth; the baby was normal at birth and remains healthy. It is concluded that the mutation at nucleotide 15923 was most likely the cause of the fatal disease in the index case. The timing of the illness was consistent with postnatal depletion of glycogen reserves. The findings suggest that a mitochondrial disorder should be considered for infants who experience sudden cardiopulmonary arrest within the first few days of life.