Mutation analysis of the methylmalonyl-CoA mutase gene in ten Mexican patients with methylmalonic acidemia

• Published in: Revista de investigacion clinica Vol. 64; no. 3; pp. 255 - 261
• Main Authors: Méndez, Sara Teresa, Vela-Amieva, Marcela, Velázquez-Arellano, Antonio, Ibarra, Isabel, Flores, María Elena
• Format: Journal Article
• Language: Spanish
• Published: Mexico 01.05.2012
• Subjects: Amino Acid Metabolism, Inborn Errors - genetics; DNA Mutational Analysis; Female; Humans; Male; Methylmalonyl-CoA Mutase - genetics; Mexico; Mexico
• ISSN: 0034-8376

Methylmalonic acidemia (MMA) is a genetically determined human metabolic disease, characterized by deficient activity of the mitochondrial enzyme, methylmalonyl CoA mutase (MCM). This enzyme catalyzes the isomerization of L-methylmalonyl CoA to succinyl CoA and requires adenosylcobalamin as cofactor. Several mutations have been identified in the unique genetic locus encoding the MCM apoenzyme (mut) which causes MMA. To identify the mutations present in Mexican patients diagnosed with MMA. Complete nucleotide sequencing of mut gene exons of 10 Mexican patients with methylmalonic acidemia (MMA) identified one novel mutation and eight mutations previously reported in the methylmalonyl-CoA mutase (mut) gene. The new mutation c.406G > T (p.V136F) was found in one patient combined with the deletion c.1891delG (p.A631QfsX17). The missense mutation c.322C > T (p.R108C) was found in six non-related patients; in addition, the mutations c.ins671-678dupAATTTATG (p.V227NfsX16), c.682C > T (p.R228X), c1022-1023dupA (p. N341KfsX20), c.1846C > T (p.R616C), c.2080C > T (p.R694W), and c.385+3insTAAGGGT (splice) were found. This work reveals that Mexican patients with MMA have new (p.V136F) as well as worldwide and hispanic reported mutations. The mutation R108C is the most frequent change (40% of total alleles) mainly in patients from León, Guanajuato.