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. MethodWe analyzed the clinical manifestation and the renal pathology of the index patient, the typeⅣ collagen in the nephridial tissue and skin by immunofluorescence, and detected theCOL4A5 gene by the next sequence method.ResultsThere 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.1365_1373del TCCAGGCCC (p.Pro456_Pro458del3) in exon 21 ofCOL4A5.Conclusions The mutation, c.1365_1373del TCCAGGCCC inCOL4A5 gene, was a novel deletion ofCOL4A5 up to now. There are many female patients in this family, antepartum gene diagnosis was necessary for them to avoid the disease reoccurring.%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IgM+，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(NM_000495)21号外显子发生缺失突变， c.1365_1373del 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1365_1373delTCCAGGCCC (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。
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