Molecular genetic basis of maple syrup urine disease in a family with two defective alleles for branched chain acyltransferase and localization of the gene to human chromosome I

W. J. Herring, S. Litwer, J. L. Weber, D. J. Danner

Research output: Contribution to journalArticlepeer-review

Abstract

Maple syrup urine disease in humans results from inherited defects in branched chain α-ketoacid dehydrogenase, a mitochondrial multienzyme complex. A variety of genetic changes may produce this phenotype by affecting the function of any of the three complex-specific subunits. The varied clinical expression observed in patients may be partially explained by the defects in the involved subunit. Here we report localization of the gene for the branched chain acyltransferase component of the complex to human chromosome 1 and describe a proband who is a compound heterozygote at this locus. One allele, inherited from the father, produces transcripts with 124 nucleotides deleted from the coding region. The deletion is not found in the branched chain acyltransferase gene, implying that the deleted transcripts arise by an error in transcript processing. Cells from the patient's mother contain 50% of the normal amount of mRNA for the subunit, and the proband has inherited this nonexpressing allele from her. As a result, the proband produces no acyltransferase protein and therefore has greatly impaired complex activity. A phenotypically normal sibling is shown to be genetically similar to the mother having inherited the mother's nonexpressing allele and the father's normal allele.

Original languageEnglish (US)
Pages (from-to)342-350
Number of pages9
JournalAmerican Journal of Human Genetics
Volume48
Issue number2
StatePublished - 1991
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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