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目的:分析一个X连锁显性遗传Alport综合征家系COL4A5基因的移码突变谱及临床表型，为该病的基因诊断和家系咨询提供基础。方法:应用二代测序技术进行基因检测，用Sanger测序对变异位点进行验证。采用病理及免疫荧光方法分别检测患者肾脏基底膜变化及COL4A5蛋白表达情况。结果:患者肾损害逐渐进展，出现肉眼血尿、蛋白尿、肾病综合征等症状，病理检测发现基底膜弥散厚薄不均，免疫荧光检测COL4A5蛋白无表达。二代测序和Sanger测序结果提示先证者COL4A5基因第41外显子存在c.3706delC(p.1236Pfs*69)的缺失变异；其母亲及两个弟弟均发现该变异。结论:报道了一个X连锁显性遗传Alport综合征家系，经基因变异筛查分析发现Ⅳ型胶原蛋白α5链的一个新的致病性基因变异，为该X连锁遗传性肾炎家系的分子诊断及临床分析提供了依据。“,”Objective:To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome.Method:Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Pathological changes of renal basement membrane and expression of COL4A5 protein were analyzed by renal biopsy and immunofluorescence, respectively.Results:All patients from the pedigree manifested progressive renal damage, gross hematuria, proteinuria and nephrotic syndrome. Renal biopsy of the proband revealed thickening of the basement membrane. No expression of the COL4A5 gene was detected by immunofluorescence. High-throughput sequencing and Sanger sequencing indicated that the proband has carried a c. 3706delC (p.1236Pfs*69) variant in exon 41 of the COL4A5 gene. The same variant was also found in his mother and two brothers whom were similarly affected.Conclusion:The novel c. 3706delC (p.1236Pfs*69) variant of the n COL4n A5 gene probably underlay the pathogenesis of X-linked hereditary Alport syndrome in this pedigree. Above findings have enriched the spectrum of COL4A5 gene variants and provided a basis for the diagnosis and genetic counseling for the pedigree.n