目的对一个临床表现酷似肥厚型心肌病的FABRY病家系进行Α半乳糖苷酶(ΑGALA)基因测序并发现其突变形式。方法该家系成员共15例,经过询问病史、体格检查、心电图及超声心动图检查,抽取外周静脉血标本,提取白细胞基因组DNA,PCR分段扩增ΑGALA基因的7个外显子序列,产物纯化后直接测序,分析筛查基因的突变位点。结果家系中有9例发生ΑGALA基因新的错义突变,突变位点位于ΑGALA基因第5外显子的第32号密码子,均由TGG变为TGA,TGA为终止密码子,故可引起TGG正常编码的色氨酸残基编码中断。其中6例女性为带有突变基因的杂合子,3例男性为带有突变基因的半合子。9例患者中6例患有心肌肥厚。家系中正常人无此类突变。结论对心肌肥厚患者应与FABRY病进行鉴别诊断。ΑGALA基因突变检测可用于FABRY病患者及其亲属,以明确诊断和进行病因学治疗。 OBJECTIVE: To sequence the A galactosidase (ΑGALA) gene of a FABRY family with clinical manifestations of hypertrophic cardiomyopathy and to find its mutated form. Methods A total of 15 pedigrees were enrolled in this study. Peripheral venous blood samples were taken from patients with history, physical examination, electrocardiogram and echocardiography to extract leukocyte genomic DNA. Seven exon sequences of ΑGALA gene were amplified by PCR and the products were purified After direct sequencing, analysis of gene mutation sites. Results There were 9 new missense mutations of ΑGALA gene in the pedigree. The mutation site was located on the 32nd codon of exon 5 of the αGALA gene. Both of them changed from TGG to TGA and TGA was the stop codon, which caused TGG Normally encoded tryptophan residues encode an interruption. Six of the women were heterozygous with the mutated gene and three of the men were hemizygous with the mutated gene. Six of the nine patients had cardiac hypertrophy. Normal families without such mutations. Conclusions Patients with cardiac hypertrophy should be differentially diagnosed with FABRY disease. ΑGALA gene mutation test can be used in patients with FABRY and their relatives to confirm the diagnosis and treatment of etiology.