functional analysis of a novel splicing mutation in the mutase gene of two unrelated pedigrees

objective: methylmalonic acidura (mma) is a rare autosomal recessive inborn error of metabolism. in this study we present a novel nucleotide change in the mutase (mut) gene of two unrelated iranian pedigrees and introduce the methods used for its functional analysis. materials and methods: two probands with definite diagnosis of mma and a common novel variant in the mut were included in a descriptive study. bioinformatic prediction of the splicing variant was done with different prediction servers. reverse transcription- polymerase chain reaction (rt-pcr) was done for splicing analysis and the products were analyzed by sequencing. results: the included index patients showed elevated levels of propionylcarnitine (c3). urine organic acid analysis confirmed the diagnosis of mma, and screening for mutations in the mut revealed a novel c to g variation at the 3´ splice acceptor site in intron 12. in silico analysis suggested the change as a mutation in a conserved sequence. the splicing analysis showed that the c to g nucleotide change at position -3 in the acceptor splice site can lead to retention of the intron 12 sequence. conclusion: this is the first report of a mutation at the position -3 in the mut intron 12 (c.2125-3c>g). the results suggest that the identified variation can be associated with the typical clinical manifestations of mma.