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目的对COL1A1和COL1A2基因突变检测为阴性的成骨不全症患者进行隐性致病基因LEPRE1的筛查。方法采集成骨不全患者外周血样,提取基因组DNA,PCR扩增LEPRE1基因,直接测序法进行突变检测;采用PolyPhen、Align GVGD和SIFT突变功能预测软件分析突变对蛋白功能的影响。结果检测到1例成骨不全症患者在LEPRE1基因第5号外显子发生碱基GGA>AGA,发现甘氨酸被精氨酸替换的1个杂合突变位点(c.1045G>A,p.Gly349Arg);其母亲和外祖父有相同杂合突变,家庭其他成员和200份健康对照样本未检测到该突变;PolyPhen、Align GVGD和SIFT软件预测结果表明,p.Gly349Arg突变很可能影响蛋白的正常功能。结论 LEPRE1基因c.1045G>A突变很可能是成骨不全症潜在的致病突变位点。
Objective To screen LEPRE1, a recessive pathogenic gene, in patients with osteogenesis imperfecta who were negative for COL1A1 and COL1A2 gene mutations. Methods Peripheral blood samples of patients with osteogenesis imperfecta were collected, genomic DNA was extracted, LEPRE1 gene was amplified by PCR and sequenced for mutation detection. PolyPhen, Align GVGD and SIFT mutation function were used to predict the effect of mutation on protein function. RESULTS: One case of osteogenesis imperfecta was found to have one heterozygous mutation site (c.1045G> A, p.Gly349Arg) in which the base GGA> AGA of LEPRE1 gene exon 5 was found to be substituted by arginine ). The same heterozygous mutation was found in both mother and grandfather. No mutation was detected in the other family members and 200 healthy controls. The prediction results of PolyPhen, Align GVGD and SIFT software showed that the mutation of p.Gly349Arg might affect the normal function of the protein. Conclusion The c.1045G> A mutation of LEPRE1 gene is likely to be a potential disease-causing mutation in osteogenesis imperfecta.