Molecular analysis of holocarboxylase synthetase deficiency: a missense mutation and a single base deletion are predominant in Japanese patients

Yoko Aoki, Yoichi Suzuki, Osamu Sakamoto, Xue Li, Kazutoshi Takahashi, Akira Ohtake, Ryoichi Sakuta, Toshihiro Ohura, Shigeaki Miyabayashi, Kuniaki Narisawa

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Holocarboxylase synthetase (HCS) deficiency is an inherited disease of biotin metabolism characterized by a unique pattern of organic aciduria, metabolic acidosis, and skin lesions. By analysis of five patients in four unrelated families, two mutations were identified: a transition from T to C which causes an amino-acid substitution of proline for leucine at position 237 (L237P) and a single deletion of guanine (delG 1067) followed by premature termination. One patient was homozygous for the L237P mutation, three patients in two families were compound heterozygotes of the missense and deletion alleles, and the other patient was heterozygous for the L237P mutation. Inheritance was successfully demonstrated in all of the patients' families by a modified PCR followed by restriction enzyme digestion. The two mutations accounted for seven of eight mutant alleles, while neither mutation was detected in 108 normal healthy Japanese children (216 alleles). Transient expression in cultured fibroblasts from a patient showed that the L237P mutation was responsible for decreased HCS activity. These results suggest that the L237P and delG1067 mutations are frequent disease-causing mutations in Japanese patients with HCS deficiency. This PCR-based technique may therefore be useful for detecting mutations among Japanese patients.

Original languageEnglish
Pages (from-to)168-174
Number of pages7
JournalBBA - Molecular Basis of Disease
Volume1272
Issue number3
DOIs
Publication statusPublished - 1995 Dec 12

Keywords

  • (Human)
  • Biotin metabolism
  • Holocarboxylase synthetase deficiency
  • Missense mutation
  • Molecular analysis
  • Single base deletion

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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