title: A novel deletion creating a new terminal exon of the dihydrolipoyl transacylase gene is a founder mutation of Filipino maple syrup urine disease.
abstract: Maple syrup urine disease (MSUD) is a rare, autosomal-recessive disorder of branched-chain amino-acid metabolism. In the Philippines, many MSUD cases have been diagnosed clinically. Here, molecular analysis of the dihydrolipoyl transacylase (E2) gene was done in 13 unrelated families from the Philippines. A novel deletion spanning 4.1 kb of intron 10 and 601 bp of exon 11, caused by non-homologous recombination between an L1 repeat in intron 10 and an Alu repeat in exon 11, was found in 8 out of 13 families, with 5 of them being homozygous for the mutation, implicating it as a founder mutation of Filipino MSUD. The resulting mutant E2 mRNA contains a 239-bp insertion after exon 10, thereby producing a new terminal exon. Large-scale population screening of the deletion revealed that one carrier of the mutation was identified in 100 normal Filipinos. These findings suggest that a limited number of mutations might underlie MSUD in the Filipino population, potentially facilitating prenatal diagnosis and carrier detection of MSUD in this group.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Catherine Lynn T
authors.initials: CL
authors.lastname: Silao
authors.forename: Carmencita D
authors.initials: CD
authors.lastname: Padilla
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000123:Acetyltransferases / Q000235:genetics*; D001483:Base Sequence; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D005091:Exons; D018703:Founder Effect; D006801:Humans; D008375:Maple Syrup Urine Disease / Q000235:genetics*; D008957:Models, Genetic; D009154:Mutation; D010679:Philippines; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D020413:3' Untranslated Regions; D011768:Pyruvate Dehydrogenase Complex; D000123:Acetyltransferases; D051047:Dihydrolipoyllysine-Residue Acetyltransferase