Hirono A, Sasaya-Hamada F, Kanno H, Fujii H, Yoshida T, Miwa S
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
Blood Cells Mol Dis. 1995;21(3):232-4. doi: 10.1006/bcmd.1995.0026.
Japanese-type acatalasemia is characterized by the almost total loss of catalase activity in red cells and is often associated with ulcerating oral lesions. A splicing mutation in intron 4 of catalase gene has so far been a sole disease-causing mutation found in Japanese-type acatalasemic patients. We report here a novel single base deletion in the catalase gene causing Japanese-type acatalasemia. The patient was a 72 year-old Japanese male. His maternal grandmother and his father were first cousins. Molecular analysis using non-RI PCR-SSCP analysis combined with direct sequencing revealed a deletion of the 358th thymine in exon 4 of the patient's catalase gene. The proband was a homozygote and his mother and his three children were heterozygotes for this mutation. The frame shift caused by the nucleotide deletion should alter the downstream amino acid sequence and introduce a new termination codon TGA 43 bp 3' to the mutation. Although the truncated peptide chain consisted of 133 amino acid residues might be translated in the patient's tissue, such an aberrant protein is expected to be extremely unstable and have no catalytic function at all. Our results suggest that Japanese-type acatalasemia is heterogeneous.
日本型无过氧化氢酶血症的特征是红细胞中过氧化氢酶活性几乎完全丧失，且常伴有口腔溃疡性病变。迄今为止，过氧化氢酶基因第4内含子中的一个剪接突变是在日本型无过氧化氢酶血症患者中发现的唯一致病突变。我们在此报告过氧化氢酶基因中一个导致日本型无过氧化氢酶血症的新型单碱基缺失。该患者为一名72岁的日本男性。他的外祖母和父亲是近亲。使用非RI PCR-SSCP分析结合直接测序的分子分析显示，患者过氧化氢酶基因第4外显子中的第358位胸腺嘧啶缺失。先证者是该突变的纯合子，他的母亲和三个孩子是杂合子。核苷酸缺失导致的移码应会改变下游氨基酸序列，并在突变位点下游43 bp处引入一个新的终止密码子TGA。尽管由133个氨基酸残基组成的截短肽链可能会在患者组织中翻译出来，但这种异常蛋白质预计极其不稳定，且完全没有催化功能。我们的结果表明，日本型无过氧化氢酶血症具有异质性。
