7个家系Wilson病同胞ATP7B基因突变分析及临床表型的研究

目的对Wilson病(WD)患病同胞进行ATP7B基因外显子测序,分析其突变的特点并探讨基因型与表型的关系。方法收集WD患病同胞的临床资料,并留取患者的外周血,提取基因组DNA,并对外显子扩增产物进行直接测序。结果 7个家系中7对同胞,共14例WD患者均检出致病突变,发现8种致病突变,包括5种错义突变,1种剪接位点突变,1种移码突变以及1种无义突变,其中,c.3851_3876del为新突变。7个家系同胞之间均为相同的基因突变形式,但同胞间临床分型不全相同,先证者临床症状多较其同胞明显,3个家系中表现为弟妹先发病。先证者与其同胞间血清铜及铜蓝蛋白水平无统计学差异。结论 WD患病同胞间基因突变形式一样,但临床分型、症状的轻重程度及发病时间可不同,WD的临床表型除了与基因突变形式有关外,还可能与其他因素相关。

Study on the mutation of ATP7B gene in 7 Wilson disease sibling patients from 7 families and the relationship between genotypes and phenotypes

Objective To examine the genotypes of the ATP7 B mutant alleles in sibling patients with Wilson disease（WD） and investigate the relationship between genotypes and phenotypes. Methods Clinical data and blood samples were collected from the subjects of sibling patients with WD. Genomic DNA was extracted and potential mutations in the exons of ATP7 B gene were detected with PCR-DNA sequencing. Results Mutations in ATP7 B were identified in 7 pairs of sibling patients from 7 unrelated families. We identified 8 different ATP7 B mutations that included 5 missense mutations, 1 splice-site mutations, 1 frameshift mutations and 1 nonsense mutations and c.3851_3876del was found to be novel. Each pair of siblings was detected to have the same mutations, but the clinical types were not all the same between them. Probands had more manifest symptoms than their siblings, and three probands was the younger among siblings, but no significant difference was found in the levels of serum copper or ceruloplasmin between them. Conclusion Same mutations as the WD sibling patients have, but the clinical type and severity of symptoms can be different; the variety of clinical manifestation between siblings may be related to another factors.