的障碍的分子基础3-methylcrotonylglycinuria亮氨酸分解代谢。
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盖拉多我,Desviat LR,罗德里格斯JM, Esparza-Gordillo J, Perez-Cerda C,佩雷斯B, Rodriguez-Pombo P, Criado O, Sanz R,莫顿DH,吉布森公里,TP,酷栗,de科尔多瓦SR Ugarte M, Penalva马
的障碍的分子基础3-methylcrotonylglycinuria亮氨酸分解代谢。
J哼麝猫。2001年2月,68(2):334 - 46所示。Epub 2001年1月17日。
- PubMed ID
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11170888 (在PubMed]
- 文摘
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3-Methylcrotonylglycinuria是一个天生的亮氨酸误差分解代谢和有一个隐性的遗传模式,结果从3-methylcrotonyl-CoA羧化酶的缺乏(MCC)。串联质谱的引入在新生儿筛查发现意外这种疾病发病率高,而在某些地区,似乎是最常见的有机酸尿。MCC, heteromeric酶α(biotin-containing)和β亚基组成,是唯一的四个biotin-dependent羧化酶在人类基因尚未特征,从而排除该疾病的分子研究。这里我们报告描述,在基因组水平和互补脱氧核糖核酸水平,MCCB的MCCA基因和基因,编码MCCα和MCCβ亚基,分别。的19-exon MCCA基因映射到3 q25-27和编码725 -残留蛋白质与生物素附件网站;的17-exon MCCB基因映射到5 q12-q13多肽和编码一个563 -残渣。我们表明,致病突变可以分为两个互补组,表示“海巡署”和“CGB。”We detected two MCCA missense mutations in CGA patients, one of which leads to absence of biotinylated MCC alpha. Two MCCB missense mutations and one splicing defect mutation leading to early MCC beta truncation were found in CGB patients. A fourth MCCB mutation also leading to early MCC beta truncation was found in two nonclassified patients. A fungal model carrying an mccA null allele has been constructed and was used to demonstrate, in vivo, the involvement of MCC in leucine catabolism. These results establish that 3-methylcrotonylglycinuria results from loss-of-function mutations in the genes encoding the alpha and beta subunits of MCC and complete the genetic characterization of the four human biotin-dependent carboxylases.