甲基丙二酸尿症（methylmalonic aciduria,MMA）又称甲基丙二酸血症,是我国最常见的有机酸代谢病,其中约70%合并同型半胱氨酸血症（合并型MMA）,30%为单纯型MMA。甲基丙二酰辅酶A变位酶（methylmalonyl coenzyme A mutase,MCM）缺陷是...甲基丙二酸尿症（methylmalonic aciduria,MMA）又称甲基丙二酸血症,是我国最常见的有机酸代谢病,其中约70%合并同型半胱氨酸血症（合并型MMA）,30%为单纯型MMA。甲基丙二酰辅酶A变位酶（methylmalonyl coenzyme A mutase,MCM）缺陷是单纯型MMA的主要病因。展开更多
Methylmalonic aciduria （MMA） is an autosomal recessive disorder of cobalamin （cbl） metabolism. Cobalamin C （cblC） disease is the most common type of MMA and is characteristically concurrent with homocystinemia ...Methylmalonic aciduria （MMA） is an autosomal recessive disorder of cobalamin （cbl） metabolism. Cobalamin C （cblC） disease is the most common type of MMA and is characteristically concurrent with homocystinemia （HCY） due to impaired synthesis of two active forms of cbl, namely adenosylcobalamin （AdoCbl） and methylcobalamin （MeCbl）. The estimated worldwide incidence of MMA ranges between 1：48,000 and 1：250,000. Mutations of the MMA and HCY type C protein （MMACtfC） gene are responsible for cblC disease and were first identified by Lerner-Ellis et aL in 2006.By the year 2016, more than 82 different MMACHC gene mutations have been reported （http：// www.hgmd.cf.ac.uk/ac/index.php）. Among these mutations, c.609G〉A （p.W203X） was reported to be the most frequent cblC mutation in Chinese patients.展开更多
Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor a...Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor adenosylcobalamin（cbl complementation groups）.The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry（GC-MS）,and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions（exon 2-13） and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424AG（p.T142A）,c.786TG（p.S262R）,c.808GC（p.G270R）,c.1323_1324insA,c.1445-1GA and c.1676＋77AC were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682CT（p.R228X） and c.323GA（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636AG（p.K212K）,c.1495GA（p.A499T）,c.1595AG（p.H532R）,c.1992GA（p.A664A）,c.2011GA（p.V671I） and c.1677-53AG were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.展开更多
文摘甲基丙二酸尿症（methylmalonic aciduria,MMA）又称甲基丙二酸血症,是我国最常见的有机酸代谢病,其中约70%合并同型半胱氨酸血症（合并型MMA）,30%为单纯型MMA。甲基丙二酰辅酶A变位酶（methylmalonyl coenzyme A mutase,MCM）缺陷是单纯型MMA的主要病因。
文摘Methylmalonic aciduria （MMA） is an autosomal recessive disorder of cobalamin （cbl） metabolism. Cobalamin C （cblC） disease is the most common type of MMA and is characteristically concurrent with homocystinemia （HCY） due to impaired synthesis of two active forms of cbl, namely adenosylcobalamin （AdoCbl） and methylcobalamin （MeCbl）. The estimated worldwide incidence of MMA ranges between 1：48,000 and 1：250,000. Mutations of the MMA and HCY type C protein （MMACtfC） gene are responsible for cblC disease and were first identified by Lerner-Ellis et aL in 2006.By the year 2016, more than 82 different MMACHC gene mutations have been reported （http：// www.hgmd.cf.ac.uk/ac/index.php）. Among these mutations, c.609G〉A （p.W203X） was reported to be the most frequent cblC mutation in Chinese patients.
基金supported by grants from the National Basic Research Program of China(2005CB522507)the 11th Five-year Plan of National Science & Technology(2006BAI05A07)
文摘Methylmalonic aciduria（MMA） is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase（MCM,mut complementation group） or in the synthesis of the MCM cofactor adenosylcobalamin（cbl complementation groups）.The defects in the mut complementation group accounts for the largest number of patients with isolated MMA.At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now.This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients.Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry（GC-MS）,and from some of their parents as well.Amplification and direct sequencing of the MUT coding regions（exon 2-13） and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations.In this group,six novel mutations in the MUT gene,c.424AG（p.T142A）,c.786TG（p.S262R）,c.808GC（p.G270R）,c.1323_1324insA,c.1445-1GA and c.1676＋77AC were identified.p.T142A and p.G270R were respectively detected at a heterozygous level in one patient.Two previously reported mutations,c.682CT（p.R228X） and c.323GA（p.R108H） were also found in this study.In addition,six previously described single nucleotide polymorphism（SNP）,c.636AG（p.K212K）,c.1495GA（p.A499T）,c.1595AG（p.H532R）,c.1992GA（p.A664A）,c.2011GA（p.V671I） and c.1677-53AG were identified.In this study,we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.
