Microarray based mutational analysis of patients with methylmalonic acidemia: Identification of 10 novel mutations

• Published in: Molecular genetics and metabolism 2012-08, Vol.106 (4), p.419-423
• Main Authors: Dündar, Halil, Özgül, Rıza Köksal, Güzel-Ozantürk, Ayşegül, Dursun, Ali, Sivri, Serap, Aliefendioğlu, Didem, Coşkun, Turgay, Tokatlı, Ayşegül
• Format: Article
• Language: English
• Subjects: Amino Acid Metabolism, Inborn Errors - enzymology; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Sequence; Amino acids; Blood; Child, Preschool; Cholesterol; DNA Mutational Analysis - methods; Fatty acids; Female; Genetic Predisposition to Disease; Hereditary diseases; Humans; Infant; Infant, Newborn; Isomerization; Male; Metabolic disorders; Methylmalonic acidemia; Methylmalonyl-CoA mutase; Methylmalonyl-CoA Mutase - chemistry; Methylmalonyl-CoA Mutase - genetics; Microarray sequencing; Molecular Sequence Data; MUT; Mutation; Mutation - genetics; Oligonucleotide Array Sequence Analysis - methods; Oxidation; Polymorphism, Genetic; Propionic acid; Sequence Alignment; succinyl-CoA; Urine
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2012.05.014

Methylmalonic acidemia is an autosomal recessive metabolic disorder affecting the propionate oxidation pathway in the catabolism of several amino acids, odd-chain fatty acids, and cholesterol. Methylmalonic acidemia is characterized by elevated levels of methylmalonic acid in the blood and urine. Mutations in the MUT gene, encoding methylmalonyl-CoA mutase carries out isomerization of L-methylmalonyl-CoA to succinyl-CoA, cause methylmalonic acidemia. In this study, 30 Turkish patients diagnosed with mut methylmalonic acidemia were screened for mutations using custom designed sequencing microarrays. The study resulted in detection of 22 different mutations, 10 of which were novel: p.Q132*, p.A137G, c.753+1T, p.T387I, p.Q514E, p.P615L, p.D625V, c.1962_1963delTC, p.L674F, and c.2115_2116insA. The most common, p.P615T, was identified in 28.0% of patients. These results suggest that microarray based sequencing is a useful tool for the detection of mutations in MUT in patients with mut methylmalonic acidemia. ► Microarray based mutation screening was performed. ► 30 Turkish patients diagnosed with mut MMA were included in the study. ► 22 different mutations, 10 of which are novel, were detected. ► The most common p.P615T mutation was identified in 28% of patients. ► Microarray sequencing is a useful tool for mutation screening in MUT gene.