Identification of a point mutation (G727T) in the glucose‐6‐phosphatase gene in Japanese patients with glycogen storage disease type 1a, and carrier screening in healthy volunteers
Identification of a point mutation (G727T) in the glucose‐6‐phosphatase gene in Japanese patients with glycogen storage disease type 1a, and carrier screening in healthy volunteers
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日本 1a 型糖原累积病患者葡萄糖-6-磷酸酶基因点突变 (G727T) 的鉴定以及健康志愿者的携带者筛查
作者：
M. Okubo;Y. Aoyama;Masahiko Kishimoto;Y. Shishiba;T. Murase
1a型糖原储存病（GSD 1a）是一种常染色体隐性代谢疾病，由葡萄糖- 6 -磷酸酶（G6Pase）缺乏引起。我们分析了两个无亲缘关系的日本GSD 1a家族的G6Pase基因。对所有5个外显子和外显子-内含子连接的DNA测序显示，外显子5的核苷酸727 （G727T）发生了G - to - T翻转，这是先前报道的导致异常剪接的原因。采用错配PCR的家庭研究显示，3例患者G727T突变为纯合子，而父母为杂合子。为了调查等位基因频率，我们筛选了216名日本健康志愿者，发现1名无症状携带者。我们的研究结果表明，G727T突变可能在日本普遍存在。
Glycogen storage disease type 1a (GSD 1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose‐6‐phosphatase (G6Pase). We analyzed the G6Pase gene of two unrelated Japanese families with GSD 1a. DNA sequencing of all five exons and exon‐intron junctions revealed a G‐to‐T transversion at nucleotide 727 (G727T) in exon 5, which has been previously reported to cause abnormal splicing. Family studies using mismatch PCR showed that three patients were homozygous for the G727T mutation, while the parents were heterozygous. To investigate allele frequencies, we screened 216 Japanese healthy volunteers and found one asymptomatic carrier. Our findings suggest that the G727T mutation may be prevalent in Japan.