Mutation Analysis of Methylmalonyl CoA Mutase Gene Exon 2 in Egyptian Families: Identification of 25 Novel Allelic VariantsDina A Ghoraba1*, Magdy M Mohammed2 and Osama K Zaki1
- *Corresponding Author:
- Dina A Ghoraba
Medical Genetics Unit
Faculty of Medicine and University Hospitals
Ain Shams University, Cairo, Egypt
E-mail: [email protected], [email protected]
Received date: June 19, 2014; Accepted date: September 08, 2014; Published date: September 15, 2014
Citation: Ghoraba DA, Mohammed MM, Zaki OK (2014) Mutation Analysis of Methylmalonyl CoA Mutase Gene Exon 2 in Egyptian Families: Identification of 25 Novel Allelic Variants. J Pharmacogenomics Pharmacoproteomics 5:139. doi: 10.4172/2153-0645.1000139
Copyright: © 2014 Ghoraba DA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Methylmalonic aciduria (MMA) is an autosomal recessive disorder of methylmalonate and cobalamin (cbl; vitamin B12) metabolism. It is an inborn error of organic acid metabolism results commonly from a defect in the gene encoding the methylmalonyl-CoA mutase apoenzyme (MCM). Here we report the results of mutation study of Exon 2 of MUT gene (coding MCM residues from 1 to 128) in ten unrelated Egyptian families affected with methylmalonic aciduria. Patients were presented with a wide-anion gap metabolic acidosis. The diagnosis has established by measurement of C3 (propionylcarnitine) and C3:C2 (propionylcarnitine/acetylcarnitine) in blood by tandem mass spectrometry, and confirmed by detection of abnormally elevated methylmalonic acid level in urine by gas chromatography-mass spectrometry GC/MS and by isocratic cation exchange “high-performance liquid-chromatography” (HPLC). Direct sequencing of gDNA of the MUT gene exon 2 has revealed a total of 26 allelic variants, ten of which were intronic, four were novel modifications predicted to affect splicing region, eight were located upstream to exon 2 coding region, three were novel mutations within coding region (c.15G>A (p.K5K), c.165C>A (p.N55K) and c.7del (p.R3EfsX14) and the last one was a previously reported mutation c.323G>A.