MAPLE-SYRUP-URINE-DISEASE (MSUD) - SCREENING FOR KNOWN MUTATIONS IN ITALIAN PATIENTS

Maple syrup urine disease (MSUD) is an autosomal recessive disease due to deficiency of the branched-chain alpha-ketoacid dehydrogenase (BCK DH) caused by a large number of mutations. In the present study, DNA f rom Italian patients and their relatives was examined for three point mutations (Y393N in the E(1 alpha) gene, T841G and G1031A in the E(2) gene) and two deletions (-G at the intron/exon border of exon 8 in the E(2) gene and an 11bp deletion in exon 1 of the E(1 beta) gene) using the polymerase chain reaction (PCR) followed by allele-specific oligo nucleotide (ASO) hybridization, gene-scanning size analysis of fluores cent-tagged PCR products and/or automated DNA sequence analysis. Our r esults show that two different mutations account for 7 of the 20 mutan t MSUD alleles, Two unrelated affected children, two of their parents and one sibling were carriers for the 11bp deletion in the E(1 beta) g ene, one patient and her mother were heterozygous for Y393N in E(1 alp ha,) while T841G, G1031A and the -G deletion in E(2) were not detected . This study is the first attempt to characterize at a nucleic acid le vel MSUD mutations in Italy. Our results indicate that additional defe cts are present in the Italian population and that, unlike the Mennoni tes, a number of different MSUD mutations exist in Italians.