Original Article | Published:

Haplotype analysis suggests that the two predominant mutations in Japanese patients with holocarboxylase synthetase deficiency are founder mutations

Journal of Human Genetics volume 45, pages 358362 (2000) | Download Citation


Holocarboxylase synthetase (HCS) deficiency is a rare autosomal recessive disorder of biotin metabolism. Including three new Japanese patients we diagnosed in this study, ten Japanese families have, so far, been accumulated. In these families, the mutations 237Leu > Pro (sevenalleles) and 1067delG (five alleles) were predominant; 508Arg > Trp and 550Val > Met mutations were identified in three families in the heterozygous form and in one patient in the homozygous form, respectively. To determine the origin of these mutations, we identified new polymorphic microsatellite markers in the HCS gene and analyzed the haplotypes of the patients. All the 237Leu > Pro and the 1067delG alleles were associated with haplotype 2-2. This finding is consistent with the notion that these mutations are founder mutations in the Japanese population. Three Japanese 508Arg > Trp alleles were associated with several haplotypes, including 2-3 and 1-4. The haplotype of a Taiwanese patient homozygous for the 508Arg > Trp mutation was 2-3/2-3. The haplotype of one Japanese patient homozygous for the 550Val > Met mutation was 1-4/1-4, whereas that of a Jewish patient with the same homozygous mutation was 2-3/2-3. Both mutations were associated with at least two haplotypes and were found in several ethnic groups. The changes 508Arg > Trp and 550Val > Met occurred at CpG dinucleotide. The data suggest that these two mutations represent a mutational hot-spot.

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  1. Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

    • Xue Yang
    • , Yoko Aoki
    • , Xue Li
    • , Osamu Sakamoto
    • , Masahiro Hiratsuka
    • , Shigeo Kure
    • , Yoichi Matsubara
    •  & Yoichi Suzuki
  2. Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, OR, USA

    • Kenneth Michael Gibson
  3. Faculty of Science and Welfare, Tohoku Bunka Gakuen University, Sendai, Japan

    • Kuniaki Narisawa


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Correspondence to Yoichi Suzuki.

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