一个β-脲基丙酸酶缺陷症家系UPB1基因新突变的分析

Identification of a novel mutation of UPB1 gene in a Chinese family affected with β-ureidopropinoase deficiency

目的对1个β-脲基丙酸酶缺陷症家系进行UPB1基因突变分析,探讨其分子遗传学病因。方法收集先证者及其家系成员外周血,提取基因组DNA,应用PCR扩增产物直接测序法对致病基因UPB1的10个外显子序列及其两侧内含子区域进行分析。采用Polyphen2及SIFT等软件对检测到的新突变进行致病性分析。结果在先证者的UPB1基因上发现第7外显子c.853G>A(P.A285T)以及第8内含子c.917-1G>A复合杂合突变,前者来自父亲,后者来自母亲。Polyphen2和SIFT软件预测突变可能致病。结论c.853G>A和c.917-1G>A复合杂合突变可能是该家系患儿的致病原因,其中c.853G>A尚未见报道,丰富了β-脲基丙酸酶缺陷症致病基因UPB1的突变谱。

Objective To explore the molecular etiology for a Chinese family affected with β-ureidopropinoase deficiency.Methods Genomic DNA was extracted from the peripheral blood samples of family members.All exons and flanking intron regions of the UPB 1 gene were amplified by PCR and detected by direct sequencing.The pathogenicity of identified mutation was analyzed using Polyphen2 and SIFT software.Results Compound heterozygous mutations of the UPB1 gene,including c.853G > A (p.A285T)and c.917-1G>A,were discovered in the proband,which were inherited respectively from his mother and father.Bioinformatics analysis suggested that this novel mutation was damaging.Conclusion The compound heterozygous mutations of the UPB 1 gene probably underlie the β-ureidopropinoase deficiency in the infant.Discovery of c.853G>A also enriched the mutation spectrum of the UPB1 gene.