Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia
Mutation spectrum of the PCCA and PCCB genes in Japanese patients with propionic acidemia
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DOI：
10.1016/j.ymgme.2004.01.003
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发表时间：
2004-04-01
影响因子：
3.8
通讯作者：
Ohura, T
中科院分区：
文献类型：
--
作者：
Yang, X;Sakamoto, O;Ohura, T
丙酸血症(PA)是由于丙酰辅酶A羧基酶缺乏而引起的一种先天性有机酸代谢错误。这种酶由两个不同的亚基组成，α和β分别由PCCA和PCCB基因编码。PCCA或PCCB的突变都可能导致酶的缺陷。为了阐明日本患者的突变谱，我们对30例PA患者进行了突变分析，其中包括9例先前报道的患者。研究表明，15例患者存在α-亚基缺陷，15例患者存在P-亚基缺陷。发现7个新突变(PCCA中的IVS18-6C>；G、1746G>；A、C398R、G197E和IVS18+IG>；A；PCCB中的A153P和IVS9+IG>；T)。在这些阿尔法亚单位缺乏的日本患者中，923-924insT、IVS18-6C>；G和R399Q突变是常见的，这三种突变加在一起的等位基因频率为56%(17/30)。这与在高加索患者中发现的突变谱形成鲜明对比，在高加索患者中还没有发现普遍的突变。在β亚基缺失中，R410W、T428I和A153P三个突变频率最高，分别为30、26.7和13.3%。总之，在日本丙酸血症患者中，PCCA和PCCB基因中的少数突变占主导地位。(C)2004 Elsevier Inc.保留所有权利。
Propionic acidemia (PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase. This enzyme is composed of two non-identical subunits, alpha and beta, which are encoded by the PCCA and PCCB genes, respectively. An enzyme deficiency can result from mutations in either PCCA or PCCB. To elucidate the mutation spectrum in Japanese patients, we have performed a mutation analysis of 30 patients with PA, which included nine previously reported patients. The study revealed that 15 patients were alpha-subunit deficient and 15 patients were P-subunit deficient. Seven novel mutations were found (IVS18 - 6C > G, 1746G > A, C398R, G197E and IVS18 + IG > A in,the PCCA; A153P and IVS9 + IG > T in the PCCB). Among these Japanese patients with alpha-subunit deficiencies, 923-924insT, IVS18 - 6C > G. and R399Q mutations were frequent and the total allelic frequency of these three mutations combined was 56% (17/30). This is in sharp contrast to the mutation spectrum found in Caucasian patients, where no prevalent mutations have been identified. Among the beta-subunit deficiencies, there were three frequent mutations; R410W, T428I, and A153P, whose allelic frequencies were 30, 26.7, and 13.3%, respectively. In conclusion, a limited number of mutations are predominant in both PCCA and PCCB genes among Japanese patients with propionic acidemia. (C) 2004 Elsevier Inc. All rights reserved.