Mutations in the holocarboxylase synthetase gene HLCS

Yoichi Suzuki, Xue Yang, Yoko Aoki, Shigeo Kure, Yoichi Matsubara

Research output: Contribution to journalReview articlepeer-review

52 Citations (Scopus)

Abstract

Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entire coding region except exons 6 and 10. The types of mutations are one single amino acid deletion, five single nucleotide insertions/deletions, 22 missense mutations, and two nonsense mutations. The only intronic mutation identified thus far is c.1519+5G> A (also designated IVS10+5G> A), which causes a splice error. Several lines of evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients. Prevalence of this mutation is about 10 times higher in the Faroe Islands than in the rest of the world. The mutations p.L237P and c.780delG are predominant only in Japanese patients. These are probably founder mutations in this population. Mutations p.R508W and p.V550M are identified in several ethic groups and accompanied with various haplotypes, suggesting that these are recurrent mutations. There is a good relationship between clinical biotin responsiveness and the residual activity of HLCS. A combination of a null mutation and a point mutation that shows less than a few percent of the normal activity results in neonatal onset. Patients who have mutant HLCS with higher residual activity develop symptom after the neonatal period and show a good clinical response to biotin therapy.

Original languageEnglish
Pages (from-to)285-290
Number of pages6
JournalHuman mutation
Volume26
Issue number4
DOIs
Publication statusPublished - 2005 Oct

Keywords

  • Biotin
  • HLCS
  • Holocarboxylase synthetase
  • Multiple carboxylase deficiency

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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