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: Catherine Lynn T Silao, Carmencita D Padilla, Masafumi Matsuo
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 81 Issue 2 Pg. 100-4 (Feb 2004) ISSN: 1096-7192 [Print] United States
• PMID: 14741190 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• Pyruvate Dehydrogenase Complex
• Acetyltransferases
• Dihydrolipoyllysine-Residue Acetyltransferase

Topics

• 3' Untranslated Regions (genetics)
• Acetyltransferases (genetics)
• Base Sequence
• Dihydrolipoyllysine-Residue Acetyltransferase
• Exons
• Founder Effect
• Humans
• Maple Syrup Urine Disease (genetics)
• Models, Genetic
• Mutation
• Philippines
• Pyruvate Dehydrogenase Complex (genetics)
• Sequence Deletion