Maple syrup urine disease

Identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population

L. Edelmann, Melissa P. Wasserstein, R. Kornreich, C. Sansaricq, S. E. Snyderman, G. A. Diaz

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Maple syrup urine disease (MSUD) is a rare, autosomal recessive disorder of branched-chain amino acid metabolism. We noted that a large proportion (10 of 34) of families with MSUD that were followed in our clinic were of Ashkenazi Jewish (AJ) descent, leading us to search for a common mutation within this group. On the basis of genotyping data suggestive of a conserved haplotype at tightly linked markers on chromosome 6q14, the BCKDHB gene encoding the E1β subunit was sequenced. Three novel mutations were identified in seven unrelated AJ patients with MSUD. The locations of the affected residues in the crystal structure of the E1β subunit suggested possible mechanisms for the deleterious effects of these mutations. Large-scale population screening of AJ individuals for R183P, the mutation present in six of seven patients, revealed that the carrier frequency of the mutant allele was ∼1/113; the patient not carrying R183P had a previously described homozygous mutation in the gene encoding the E2 subunit. These findings suggested that a limited number of mutations might underlie MSUD in the AJ population, potentially facilitating prenatal diagnosis and carrier detection of MSUD in this group.

Original languageEnglish (US)
Pages (from-to)863-868
Number of pages6
JournalAmerican Journal of Human Genetics
Volume69
Issue number4
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Maple Syrup Urine Disease
Mutation
Population
Branched Chain Amino Acids
Prenatal Diagnosis
Genetic Markers
Gene Frequency
Haplotypes
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Maple syrup urine disease : Identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population. / Edelmann, L.; Wasserstein, Melissa P.; Kornreich, R.; Sansaricq, C.; Snyderman, S. E.; Diaz, G. A.

In: American Journal of Human Genetics, Vol. 69, No. 4, 2001, p. 863-868.

Research output: Contribution to journalArticle

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