Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia

Keyfi, F. and Abbaszadegan, M. R. and Rolfs, A. and Orolicki, S. and Moghaddassian, M. and Varasteh, A. (2016) Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia. Cellular and Molecular Biology Letters, 21 (1).

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Background: Adenosylcobalamin (vitamin B12) is a coenzyme required for the activity of methylmalonyl-CoA mutase. Defects in this enzyme are a cause of methylmalonic acidemia (MMA). Methylmalonic acidemia, cblA type, is an inborn error of vitamin B12 metabolism that occurs due to mutations in the MMAA gene. MMAA encodes the enzyme which is involved in translocation of cobalamin into the mitochondria. Methods: One family with two MMA-affected children, one unaffected child, and their parents were studied. The two affected children were diagnosed by urine organic acid analysis using gas chromatography-mass spectrometry. MMAA was analyzed by PCR and sequencing of its coding region. Results: A homozygous deletion in exon 4 of MMAA, c.674delA, was found in both affected children. This deletion causes a nucleotide frame shift resulting in a change from asparagine to methionine at amino acid 225 (p.N225M) and a truncated protein which loses the ArgK conserved domain site. mRNA expression analysis of MMAA confirmed these results. Conclusion: We demonstrate that the deletion in exon 4 of the MMAA gene (c.674 delA) is a pathogenic allele via a nucleotide frame shift resulting in a stop codon and termination of protein synthesis 38 nucleotides (12 amino acids) downstream of the deletion. © 2016 The Author(s).

Item Type: Article
Additional Information: Cited By :5 Export Date: 16 February 2020 CODEN: CMBLF Correspondence Address: Varasteh, A.; Mashhad University of Medical Sciences, Allergy Research CenterIran; email:
Uncontrolled Keywords: Biochemical analysis Cobalamin Methylmalonic acidemia MMAA gene Mutation analysis Novel deletion Structural analysis Vitamin B12 ammonia benzoic acid bicarbonate carnitine citrate sodium citric acid hydroxocobalamin lactic acid messenger RNA metronidazole propionylcarnitine pyruvic acid Shohl solution unclassified drug carrier protein cyanocobalamin MMAA protein, human ammonia blood level anorexia Article bicarbonate blood level case report cause of death child developmental delay developmental disorder enzyme blood level exon failure to thrive female gene deletion gene expression gene identification gene mutation gene sequence hemodialysis hepatomegaly homozygote hospital admission hospitalization human informed consent Iranian people lactate blood level lethargy male mass fragmentography muscle hypotonia pH preschool child protein restriction real time polymerase chain reaction tandem mass spectrometry urinalysis urine organic acid analysis vomiting disorders of amino acid and protein metabolism enzymology frameshift mutation genetics indel mutation infant Iran metabolism nucleotide sequence pedigree protein tertiary structure sibling Amino Acid Metabolism, Inborn Errors Base Sequence Child, Preschool Humans Mitochondrial Membrane Transport Proteins Protein Structure, Tertiary Siblings Vitamin B 12
Subjects: QW Microbiology and Immunology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib4 lib4
Date Deposited: 02 Mar 2020 04:12
Last Modified: 02 Mar 2020 04:12

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