Cargando…

Mutation analysis of methylmalonyl CoA mutase gene exon 2 in Egyptian families: Identification of 25 novel allelic variants

Methylmalonic aciduria (MMA) is an autosomal recessive disorder of methylmalonate and cobalamin (cbl; vitamin B(12)) metabolism. It is an inborn error of organic acid metabolism which commonly results from a defect in the gene encoding the methylmalonyl-CoA mutase (MCM) apoenzyme. Here we report the...

Descripción completa

Detalles Bibliográficos
Autores principales: Ghoraba, Dina A., Mohammed, Magdy M., Zaki, Osama K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349194/
https://www.ncbi.nlm.nih.gov/pubmed/25750861
http://dx.doi.org/10.1016/j.mgene.2014.02.001
Descripción
Sumario:Methylmalonic aciduria (MMA) is an autosomal recessive disorder of methylmalonate and cobalamin (cbl; vitamin B(12)) metabolism. It is an inborn error of organic acid metabolism which commonly results from a defect in the gene encoding the methylmalonyl-CoA mutase (MCM) apoenzyme. Here we report the results of mutation study of exon 2 of the methylmalonyl CoA mutase (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 the measurement of C3 (propionylcarnitine) and C3:C2 (propionylcarnitine/acetylcarnitine) in blood by using liquid chromatography–tandem mass spectrometry (LC/MS–MS) and was confirmed by the detection of an abnormally elevated level of methylmalonic acid in urine by using gas chromatography–mass spectrometry (GC/MS) and 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, eight were located upstream to the exon 2 coding region, four were novel modifications predicted to affect the splicing region, three were novel mutations within the coding region: c.15G > A (p.K5K), c.165C > A (p.N55K) and c.7del (p.R3EfsX14), as well as the previously reported mutation c.323G > A (p.R108H).