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目的 了解中国人戈谢病 (GD)基因型及其与临床表型的相关性。方法 10例中国GD患儿 (男 9,女 1。其中 5例Ⅰ型 ,2例Ⅱ型 ,3例Ⅲ型 ) ,来自无关的家庭 ,年龄 1 5～ 13岁。所有GD患儿的诊断是根据白细胞或成纤维细胞中 β 葡萄糖苷酶活性明显缺乏及骨髓象中出现戈谢细胞确定。采用巢氏聚合酶链反应扩增葡萄糖脑苷脂酶功能基因 ,产物覆盖了全部编码区 ;再分别扩增 11个外显子 ,用于限制酶切片断多态性 (RLFP) ,单链构像多态性 (SSCP)及序列分析。结果 5例Ⅰ型GD患儿的基因型是R48W R12 0W、G46E L44 4P、F37V L44 4P、N188S L44 4P及Y2 0 5C L44 4P ;2例Ⅱ型GD均为F2 13I L44 4P ;3例Ⅲ型GD为D40 9H D40 9H、G2 0 2R D40 9H及L44 4P L44 4P。检出了 2个新生突变F37V及Y2 0 5C。结论 中国GD患儿的L44 4P突变的等位基因频率最高 (40 % )。它同时出现在有神经病变及无神经病变的表型中。F2 13I、D40 9H及G2 0 2R突变基因型与有神经病变表型相关。
Objective To understand the Chinese genotypes of Gaucher disease (GD) and its relationship with clinical phenotypes. Methods Ten Chinese children with GD (male 9, female 1. 5 cases of type Ⅰ, 2 cases of type Ⅱ, 3 cases of type Ⅲ) were from unrelated families, aged 15 to 13 years. Diagnosis of all children with GD is based on the apparent lack of beta-glucosidase activity in leukocytes or fibroblasts and the presence of Goose’s cells in the bone marrow. The nested PCR amplification of glucocerebrosidase gene, the product covers the entire coding region; and then amplified 11 exons, respectively, for restriction fragment analysis of polymorphisms (RLFP), single-strand conformation Like polymorphism (SSCP) and sequence analysis. Results The genotypes of five cases of type Ⅰ GD were R48W R12 0W, G46E L44 4P, F37V L44 4P, N188S L44 4P and Y2 05C L44 4P. Two cases of type Ⅱ GD were F2 13I L44 4P. Three cases of type Ⅲ GD is D40 9H D40 9H, G2 0 2R D40 9H and L44 4P L44 4P. Two newborn mutations, F37V and Y2 0 5C, were detected. Conclusion The allele frequency of L44 4P mutation in Chinese children with GD is the highest (40%). It appears in both neuropathies and neuropathies. The F2 13I, D40 9H and G2 0 2R mutant genotypes were associated with a neuropathic phenotype.