Glucose‐6‐phosphatase gene (727G→T) splicing mutation is prevalent in Hong Kong Chinese patients with glycogen storage disease type la
Glucose‐6‐phosphatase gene (727G→T) splicing mutation is prevalent in Hong Kong Chinese patients with glycogen storage disease type la
复制标题
葡萄糖-6-磷酸酶基因（727G→T）剪接突变在中国香港糖原贮积症la型患者中普遍存在
作者：
C. Lam;W. But;C. Shek;S. Tong;Y. Chan;K. Choy;W. Tse;C. Pang;N. M. Hjelm
糖原沉积病1a(GSD1a)是由葡萄糖-6-磷酸酶(GóPase)缺乏引起的一种常染色体隐性代谢性疾病。我们分析了两个无血缘关系的GSD1a中国家系的GóPase基因。所有5个外显子和外显子边界的DNA测序显示，外显子5的第727位核苷酸(727G→T)存在G→T颠换，这是先前报道的导致异常剪接的原因。在一个家庭中，受试者和她受影响的妹妹被证实为该突变的纯合子，他们的父母是杂合子。在另一个家系中，先证者被确认为该突变的杂合子，并发现了一个新的突变，即外显子2的341delG。这种突变改变了阅读框架，并在突变下游产生了一个终止密码子TAA 15密码子，导致蛋白质被截断。家族研究显示，父亲是727G→T突变的杂合子，母亲是341 delG突变的杂合子。这是首次在中国或日本以外的患者中发现727G→T突变。由于我们只检测了两个GSDla家系，并在两个家系中都发现了727G→T，我们认为这种突变可能也在我们当地的中国人中流行。为了调查等位基因频率，我们对385名中国健康志愿者进行了筛查，发现了两名无症状携带者。我们的发现表明，727G→T突变在香港确实很常见。
Glycogen storage disease type la (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose‐6‐phosphatase (GóPase). We analyzed the GóPase genes of two unrelated Chinese families with GSD1a. DNA sequencing of all five exons and the exonintron boundaries revealed a G → T transversion at nucleotide 727 (727G→T) in exon 5, which has previously been reported to cause abnormal splicing. In one family, the subject and her affected sister were confirmed to be homozygous for this mutation and their parents to be heterozygotes. In the other family, the proband was identified to be heterozygous for this mutation, and a novel mutation, the 341delG in exon 2, was identified. This mutation alters the reading frame and creates a stop codon TAA 15 codons downstream from the mutation, resulting in a truncated protein. Family studies revealed that the father was heterozygous for the 727G → T mutation and that the mother was heterozygous for the 341delG mutation. This is the first time that the 727G→T mutation has been found in Chinese patients or outside Japan. Since we only tested two GSDla families and found 727G→T in both, we believe that this mutation may also be prevalent in our local Chinese population. To investigate allele frequencies, we screened 385 Chinese healthy volunteers and found two asymptomatic carriers. Our findings suggest that the 727G → T mutation is indeed prevalent in Hong Kong.