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Mutation Profile of the MUT Gene in Chinese Methylmalonic Aciduria Patients

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JIMD Reports - Case and Research Reports, 2012/3


The mut-type methylmalonic aciduria (MMA, MIM 251000) is caused by a deficiency of mitochondrial methylmalonyl-CoA mutase (MCM, E.C. activity, which results from defects in the MUT gene. To elucidate the mutation spectrum of the MUT gene in Chinese MMA patients, 13 exons of the MUT gene, including untranslated regions, were analyzed by PCR-based sequencing for 42 unrelated Chinese MMA patients. All the 42 patients were found to have at least one MUT mutation. A total of 41 mutations were identified. Of these mutations, 20 were novel ones, including one nonsense mutation (c.103C>T), 12 missense mutations (c.316A>C, c.424A>G, c.494A>G, c.554C>T, c.599T>C, c.919T>C, c.1009T>C, c.1061C>T, c.1141G>A, c.1208G>A, c.1267G>A, and c.1295A>C), one duplication (c.755dupA), three small deletions (c.398_399delGA, c.1046_1058del, and c.1835delG), two mutations that might affect mRNA splicing (c.754-1G>A and c.1084-10A>G), and one major deletion. Among the mutations identified, the c.1280G>A (15.5%), c.729_730insTT (10.7%), c.1106G>A (4.8%), c.1630_1631GG>TA (4.8%), and c.2080C>T (4.8%) accounted for 40% of the diseased alleles. The c.1280G>A and c.729_730insTT mutations were found to be the most frequent mutations in Southern and Northern Chinese, respectively. The results of microsatellite analysis suggest that the spread of c.729_730insTT among the Northern Chinese and of c.1280G>A and c.1630_1631GG>TA among the Southern Chinese may have undergone founder effects. This mutation analysis of the gene responsible for mut-type MMA will help to provide a molecular diagnostic aid for differential diagnosis of MMA and could be applied for carrier detection and prenatal diagnosis among Chinese family at risk of mut-type MMA.

Competing interests: None declared

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Methylmalonyl-CoA mutase


Methylmalonic aciduria


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The authors thank Sequencing Core of Genome Research Center of National Yang-Ming University for sequencing works and Dr. S.-F. Tsai for discussion and various helpful suggestions. This study was partially supported by the National Health Research Institutes and, in part, by grants from the National Science Council (NSC92-2320-B-010-076) and the Bureau of Health Promotion, Department of Health (DOH94-HP-2204 and DOH95-HP-2206), Taiwan, Republic of China.

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Correspondence to Kwang-Jen Hsiao .

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Communicated by: Ivo Baric

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Contribution of Individual Authors



Mei-Ying Liu

Plan, conduct, and prepare this manuscript

Tze-Tze Liu

Plan, supervise, discuss, and prepare this manuscript

Yan-Ling Yang

Clinical diagnosis and collection of clinical information

Shu-Fen Lee

Conduct experiments

Yu-Ting Teng

Conduct experiments

Ying-Chen Chang

Conduct the molecular genetics study

Ya-Ling Fan

Biochemical and enzymatic studies

Szu-Hui Chiang

Collection of information

Dau-Ming Niu

Clinical diagnosis and collection of clinical information

Shio-Jean Lin

Clinical diagnosis and collection of clinical information

Mei-Chun Chao

Clinical diagnosis and collection of clinical information

Shuan-Pei Lin

Clinical diagnosis and collection of clinical information

Lian-Shu Han

Clinical diagnosis and collection of clinical information

Yu Qi

Collection and establishment of cell lines

Kwang-Jen Hsiao*

Plan, supervise, discussion, and prepare this manuscript

Statement of Competing Interest

The authors have nothing to declare.

Details of the Ethics Approval

Partial patients were retrospectively studied. This study was approved by the Ethics Committee of the Taipei Veterans General Hospital.

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© 2012 SSIEM and Springer-Verlag Berlin Heidelberg

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Liu, MY. et al. (2012). Mutation Profile of the MUT Gene in Chinese Methylmalonic Aciduria Patients. In: JIMD Reports - Case and Research Reports, 2012/3. JIMD Reports, vol 6. Springer, Berlin, Heidelberg.

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