Confirmation that MAT1A p.Ala259Val mutation causes autosomal dominant hypermethioninemia

摘要

Abstract Methionine adenosyltransferase (MAT) I/III deficiency is an inborn error of metabolism caused by mutations in MAT1A, encoding the catalytic subunit of {MAT} responsible for the synthesis of S-adenosylmethionine, and is characterized by persistent hypermethioninemia. While historically considered a recessive disorder, a milder autosomal dominant form of {MAT} I/III deficiency occurs, though only the most common mutation p.Arg264His has ample evidence to prove dominant inheritance. We report a case of hypermethioninemia caused by the p.Ala259Val substitution and provide evidence of autosomal dominant inheritance by showing both maternal inheritance of the mutation and concomitant hypermethioninemia. The p.Ala259Val mutation falls in the dimer interface, and thus likely leads to dominant inheritance by a similar mechanism to that described in the previously reported dominant negative mutation, that is, by means of interference with subunits encoded by the wild-type allele.