Clinical characteristics and gene mutation analysis of methylmalonic aciduria |
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Authors: | Qin Yi Juanjuan Lv Fengyan Tian Hong Wei Qin Ning Xiaoping Luo |
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Institution: | 1. Department of Pediatrics,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 2. Department of Infectious Disease,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China |
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Abstract: | 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.424A>G (p.T142A), c.786T>G (p.S262R), c.808G>C (p.G270R), c.1323_1324insA, c.1445-1G>A and c.1676+77A>C
were identified. p.T142A and p.G270R were respectively detected at a heterozygous level in one patient. Two previously reported
mutations, c.682C>T (p.R228X) and c.323G>A (p.R108H) were also found in this study. In addition, six previously described
single nucleotide polymorphism (SNP), c.636A>G (p.K212K), c.1495G>A (p.A499T), c.1595A>G (p.H532R), c.1992G>A (p.A664A), c.2011G>A
(p.V671I) and c.1677-53A>G were identified. In this study, we updated the spectrum of MUT mutations and identified the main
MMA-causing mutations in Chinese MMA patients. |
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Keywords: | methylmalonic aciduria MUT gene gene mutation single nucleotide polymorphism |
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