Maple syrup urine disease (MSUD) is an autosomal recessive disease due to deficiency of the branched-chain α-ketoacid dehydrogenase (BCKDH) caused by a large number of mutations. In the present study, DNA from Italian patients and their relatives was examined for three point mutations (Y393N in the E1α gene, T841G and G1031A in the E2 gene) and two deletions (-G at the intron/exon border of exon 8 in the E2 gene and an 11 bp deletion in exon 1 of the E1β gene) using the polymerase chain reaction (PCR) followed by allele-specific oligonucleotide (ASO) hybridization, gene-scanning size analysis of fluorescent-tagged PCR products and/or automated DNA sequence analysis. Our results show that two different mutations account for 7 of the 20 mutant MSUD alleles. Two unrelated affected children, two of their parents and one sibling were carriers for the 11 bp deletion in the E1β gene, one patient and her mother were heterozygous for Y393N in E1α, while T841G, G1031A and the -G deletion in E2 were not detected. This study is the first attempt to characterize at a nucleic acid level MSUD mutations in Italy. Our results indicate that additional defects are present in the Italian population and that, unlike the Mennonites, a number of different MSUD mutations exist in Italians.
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