Molecular Analysis of The Methylmalonyl-COA Mutase Gene in The Egyptian Patients with Methylmalonic Acidemia

Abstract

Methylmalonic acidemia (MMA) is an autosomal recessive inherited inborn error of metabolism that results from the functional impairment of methylmalonyl-CoA mutase (MCM). The impairment of MCM is due to either defect in the apoenzyme (mut-type MMA) or in biosynthesis of the cofactor, adenosylcobalamin (cbl type). To examine the mutation spectrum of the MUT gene of Egyptian patients with mut MMA, entire length of MUT mRNA, specially coding region, was amplified and analyzed for 15 unrelated Egyptian MMA patients. A total of 12 mutations, 10 in coding region and 2 in untranslated region, were identified. Of these 10 mutations, 5 were missense mutations, 3 were nonsense mutations, 1 was deletion mutation and 1 was synonymous mutation. One novel mutation c.1420 C>T (p.Arg474*) in exon 7 was identified in this study and other mutations have been reported previously. Identification of these mutations in MMA Egyptian patients will facilitate differential confirmatory diagnosis, which is important for appropriate treatments. It will also aid carrier detection, genetic counseling,