【摘要】 目的对表现为家族性血尿并伴性遗传的Alport综合征家系进行临床及基因研究,以发现其可能的致病基因及致病位点。方法肾穿刺明确病理类型,肾组织及皮肤Ⅳ型胶原染色,外显子测序方法进行基因测序及验证,同时对患者的血及尿液进行分析。结果对该家系中7个患病者进行研究,血尿表现为肉眼血尿,无眼及耳损害,已有两人肾功能衰竭,其中一人肾移植,先证者男性肾脏病理表现为系膜增生性病变,电镜下基底膜无增厚或变薄,免疫荧光Ig M+,但Ⅳ型胶原免疫荧光无缺失。通过二代测序技术,发现先证者COL4A5（NM₀00495）21号外显子发生缺失突变,c.1365₁373del TCCAGGCCC（p.Pro456_Pro458del3）,较之野生型蛋白的1685个氨基酸,突变型蛋白仅有1682个氨基酸。先证者双胞胎兄及表兄患者存在相同突变。其母及姨母为杂合缺失。先证者之父及外祖父为正常,表明该家系存在基因型表型共分离。对正常对照100例及散发病例未发现该突变,说明突变频率较低。结论本研究利用基因测序法对一Alport综合征家系进行研究,发现了新的COL4A5基因1365₁373del TCCAGGCCC（p.Pro456_Pro458del3）胶原区缺失突变。家族中有多例女性患者,再生育风险较大。更多还原

【Abstract】 Objective To investigate the clinical and genetic diagnosis of a Chinese family with hematuria, which displayed sex-linked hereditary, so that we can find the virulence gene and sites.Method We analyzed the clinical manifestation and the renal pathology of the index patient, the type Ⅳ collagen in the nephridial tissue and skin by immunofluorescence, and detected the COL4A5 gene by the next sequence method. Results There were 7 patients in the family, they all showed gross hematuri, two of them had progressed to end-stage renal disease（ERDS）, but none of them were involved in eye or ear damage.There was no special lesion of the glomcrulus;the GBM was normal with a normal thickness; by next sequencing we found a mutation of c.1365₁373del TCCAGGCCC（p.Pro456_Pro458del3） in exon 21 of COL4A5.Conclusions The mutation, c.1365₁373del TCCAGGCCC in COL4A5 gene, was a novel deletion of COL4A5 up to now. There are many female patients in this family, antepartum gene diagnosis was necessary for them to avoid the disease reoccurring.更多还原