克隆人类MCCA MCCB基因和突变就揭示了分子的原因3-methylcrotonyl-CoA:羧化酶缺乏症。
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Holzinger, Roschinger W, Lagler F, Mayerhofer PU、Lichtner P, Kattenfeld T, Thuy LP尼汉西城,科赫HG, Muntau AC,罗斯奇AA
克隆人类MCCA MCCB基因和突变就揭示了分子的原因3-methylcrotonyl-CoA:羧化酶缺乏症。
哼摩尔麝猫。2001年6月1;10 (12):1299 - 306。
- PubMed ID
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11406611 (在PubMed]
- 文摘
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3-Methylcrotonyl-CoA:羧化酶(EC 6.4.1.4;MCC)缺乏是一个天生的错误亮氨酸的降解途径(MIM * 210200)以增加3-hydroxyisovaleric酸和3-methylcrotonylglycine的尿排泄。临床表型是高度变量从无症状到深刻的代谢性酸中毒和死亡阶段。序列相似性与大豆和拟南芥基因编码的两个子单元MCC允许我们克隆的互补编码人类MCC的α-和beta-subunits。2580年英国石油公司MCCA cDNA编码725个氨基酸biotin-containing alpha-subunit。MCCA基因位于染色体3 q26-q28,由19个外显子。2304年英国石油公司MCCB cDNA编码non-biotin-containing beta-subunit 563氨基酸。MCCB基因位于5号染色体问题,由17个外显子。我们有两个基因测序在四个患者孤立biotin-unresponsive MCC的不足。在其中两个我们发现MCCA基因的突变。 Compound heterozygosity for a missense mutation (S535F) and a nonsense mutation (V694X) were identified in one patient. One heterozygous mutation (S535F) was found in another patient. The remaining two patients had mutations in the MCCB gene. One consanguineous patient was homozygous for a missense mutation (R268T). In the other we identified a missense mutation in one allele (E99Q) and allelic loss of the other. Mutations were correlated with an almost total lack of enzyme activity in fibroblasts. These data provide evidence that human MCC deficiency is caused by mutations in either the MCCA or MCCB gene.