Clustering of mutations in the biotin-binding region of holocarboxylase synthetase in biotin-responsive multiple carboxylase deficiency

Lucie Dupuis, Alfonso Leon-Del-Rio, Daniel Leclerc, Eric Campeau, Lawrence Sweetman, Jean Marie Saudubray, Gail Herman, K. Michael Gibson, Roy A. Gravel

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Holocarboxylase synthetase (HCS) catalyses the biotinylation of the four biotin-dependent carboxylases found in humans. A deficiency in HCS results in biotin-responsive multiple carboxylase deficiency (MCD). We have identified six different point mutations in the HCS gene in nine patients with MCD. Two of the mutations are frequent among the MCD patients analyzed. Four of the mutations cluster in the putative biotin-binding domain as deduced from the corresponding Escherichia coli enzyme and consistent with an explanation for biotin-responsiveness based on altered affinity for biotin. The two others may define an additional domain involved in biotin-binding or biotin-mediated stabilization of the protein.

Original languageEnglish (US)
Pages (from-to)1011-1016
Number of pages6
JournalHuman molecular genetics
Volume5
Issue number7
DOIs
StatePublished - Jul 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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