Kawame H, Eto Y
Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan.
Am J Hum Genet. 1991 Dec;49(6):1378-80.
We have identified a new T-to-A single-base substitution at nucleotide 3548 (in the genomic sequence) in exon 6 in the glucocerebrosidase gene from a patient with Gaucher disease type 3. This mutation caused a substitution of isoleucine for phenylalanine at amino acid residue 213 (of 497 residues in the mature protein). By in vitro expression study in cultured mammalian cells, this mutation resulted in deficient activity of glucocerebrosidase. By allele-specific oligonucleotide hybridization of selectively PCR-amplified DNA from eight unrelated Japanese Gaucher disease patients, this mutant allele was observed in other neuronopathic Japanese Gaucher disease patients, in moderately frequent occurrence (three of six neuronopathic patients). This observation suggests that this allele was one of severe [corrected] alleles which were related to the development of neurological manifestations of Gaucher disease.
我们在一名3型戈谢病患者的葡萄糖脑苷脂酶基因第6外显子（基因组序列）的3548位核苷酸处鉴定出一个新的T到A单碱基替换。该突变导致成熟蛋白497个氨基酸残基中的第213位氨基酸由苯丙氨酸替换为异亮氨酸。通过在培养的哺乳动物细胞中进行体外表达研究，该突变导致葡萄糖脑苷脂酶活性不足。通过对8名无关的日本戈谢病患者选择性PCR扩增的DNA进行等位基因特异性寡核苷酸杂交，在其他神经病变型日本戈谢病患者中观察到该突变等位基因，出现频率中等（6名神经病变患者中有3名）。这一观察结果表明，该等位基因是与戈谢病神经学表现发展相关的严重[校正后]等位基因之一。
