Abstract
Methylmalonic acidemia (MMA) is caused by a deficiency in the activity of l-methylmalonyl-CoA mutase (MCM), a vitamin B12 (or cobalamin, Cbl)-dependent enzyme. Apoenzyme-deficient MMA (mut MMA) results from mutations in the nuclear gene MUT. Most of the MUT mutations are thought to be private or restricted to only a few pedigrees. Our group elucidated the spectrum of mutations of Japanese mut MMA patients by performing mutation and haplotype analyses in 29 patients with mut MMA. A sequence analysis identified mutations in 95% (55/58) of the disease alleles. Five mutations were relatively frequent (p.E117X, c.385 + 5G > A, p.R369H, p.L494X, and p.R727X) and four were novel (p.M1V, c.753_753 + 5delGGTATA, c.1560G > C, and c.2098_2099delAT). Haplotype analysis suggested that all of the frequent mutations, with the exception of p.R369H, were spread by the founder effect. Among 46 Japanese patients investigated in the present and previous studies, 76% (70/92) of the mutations were located in exons 2, 6, 8, and 13. This finding – that a limited number of mutations account for most of the mutations in Japanese mut MMA patients – is in contrast with results of a previous study in Caucasian patients.
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Acknowledgments
We thank all of the physicians who provided samples and/or clinical and biochemical data on their patients. We also express our gratitude to Dr. F. Kok (University of Sao Paulo) for providing us with dried blood samples This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and the Morinaga Hoshikai Foundation.
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Sakamoto, O., Ohura, T., Matsubara, Y. et al. Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia. J Hum Genet 52, 48–55 (2007). https://doi.org/10.1007/s10038-006-0077-2
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DOI: https://doi.org/10.1007/s10038-006-0077-2
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