Microarray based mutational analysis of patients with methylmalonic acidemia: identification of 10 novel mutations.
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.
Metabolism Unit, Department of Pediatrics, Hacettepe University, Ankara, Turkey.
Halil
H
Dündar
Riza Köksal
RK
Özgül
Ayşegül
A
Güzel-Ozantürk
Ali
A
Dursun
Serap
S
Sivri
Didem
D
Aliefendioğlu
Turgay
T
Coşkun
Ayşegül
A
Tokatli
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D000595:Amino Acid Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008765:Methylmalonyl-CoA Mutase / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011110:Polymorphism, Genetic; D016415:Sequence Alignment
D008765:Methylmalonyl-CoA Mutase