Genetic analysis of isolated persistent hypermethioninemia with dominant inheritance

We describe a type of mild hypermethioninemia due to a point mutation in the MATA1 gene, which was inherited dominantly in a family. Three patients coming from the same family pedigree were detected by the presence of isolated hypermethioninemia on a mass-screening program. The measurement of methionine adenosyltransferase (MAT) activity in a patient's liver revealed a partial deficiency of hepatic MAT with a reduction in the Km for methionine. Single strand conformation polymorphism (SSCP) analysis and direct sequencing of the patients' genomic DNA revealed a G to A mutation at nucleotide 791 that converts Arg-264 to His (R264H) in one allele of MATA1 gene. The other allele was normal in all the patients examined. Gene tracking in the family revealed that the hypermethioninemia is associated with heterozygosity for the R264H mutation in the MATA1 gene.