Abstract
The cblC type of combined methylmalonic aciduria (MMA) and homocystinuria (HC) is the most common inborn error of vitamin B12 metabolism and is caused by mutations in the MMACHC gene. To elucidate the spectrum of mutations that causes combined MMA and HC in Chinese patients, the MMACHC gene was sequenced in 79 unrelated Chinese patients. Sequence analysis identified 98.1% of disease alleles and found that all patients had at least one MMACHC mutation. A total of 24 mutations were identified. Out of the 24 mutations identified, 9 were novel ones, including missense mutations (c.365A>T and c.452A>G), nonsense mutations (c.315C>G and c.615C>A), deletions (c.99delA and c.277-3_c.303del30), duplications (c.248dupT and c.626dupT) and an insertion (c.445_446insA). The c.609G>A, c.658_660delAAG, c.482G>A, c.394C>T and c.80A>G mutations were the most common mutations and accounted for 80% of disease alleles. Haplotype analysis suggests that the spread of the c.80A>G, c.609G>A and c.658_660delAAG mutations in Chinese patients were caused by a founder effect. The results indicate that defects occurring in the MMACHC gene are the major cause of this disease in Chinese patients with combined MMA and HC, and direct mutation analysis can therefore be used as a rapid confirmatory diagnosis among these Chinese patients.
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Acknowledgements
We thank the Sequencing Core of Genome Research Center of the National Yang-Ming University for sequencing works and Dr Tsai, S.-F. for discussions and various helpful suggestions. This work was partially supported by the National Health Research Institutes and grants from the Bureau of Health Promotion, Department of Health (DOH94-HP-2204 and DOH95-HP-2206), Taiwan, Republic of China.
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Liu, MY., Yang, YL., Chang, YC. et al. Mutation spectrum of MMACHC in Chinese patients with combined methylmalonic aciduria and homocystinuria. J Hum Genet 55, 621–626 (2010). https://doi.org/10.1038/jhg.2010.81
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DOI: https://doi.org/10.1038/jhg.2010.81
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