COL4A5基因新发突变致ALPORT综合征1例并文献复习

ALPORT SYNDROME CAUSED BY A NOVEL MUTATION IN THE COL4A5 GENE:A CASE REPORT AND LITERATURE REVIEW

目的报道1例COL4A5基因新发突变致ALPORT综合征患者,探讨该病的临床表现及遗传学特征。方法收集患者的临床资料,提取外周血DNA,通过全外显子组测序技术检测患儿及直系亲属COL4A5基因突变情况,并结合HGMD数据库中相关文献进行复习。结果患者长期反复血尿、蛋白尿,糖皮质激素治疗无效;肾脏穿刺活检,光镜下检查显示肾小球节段系膜轻度增生性病变;电镜检查显示肾小球基底膜厚薄不一,基底膜致密层增厚,部分呈撕裂状和蛛网状;基因检测显示患者COL4A5基因第38号外显子编码区第3393~3419位碱基缺失(c.3393_3419del),导致第1128~1136号氨基酸缺失(p.G1128_S1136del);家系验证其为新发突变,且该突变位点在HGMD等数据库中均未见报道。入院后继续给予福辛普利钠治疗,以减少尿蛋白分泌、延缓肾脏病变。随访半年余,患儿无听力及眼部异常改变,肾功能无异常。结论COL4A5基因c.3393_3419del突变可能导致ALPORT综合征。早期的肾脏病理检查及基因检测对于明确ALPORT综合征的诊断、治疗方案的制定以及预后的评估具有重要意义。

Objective To report a case of ALPORT syndrome caused by a novel mutation in the COL4A5 gene,and to explore the clinical manifestations and genetic features of the disease.Methods The clinical data of the child were collected,and the peripheral blood DNA was extracted.COL4A5 gene mutation of the child and his immediate family members was detected by the whole exome sequencing technology,and the relevant literature data in the Human Gene Mutation Database(HGMD)were reviewed.Results The patient suffered from chronic repeated hematuria and proteinuria,and showed no response to glucocorticoid therapy.His kidney biopsy under a light microscope showed mild hyperplastic lesions in the mesangium of the glomerular segment.Electron microscopy showed that the thickness of the glomerular basement membrane was variable,and the dense layer of the basement membrane was thickened,partially torn and cobwebbed.Genetic testing revealed base deletion at the sites 3393-3419 in the coding region of exon 38 of the patient’s COL4A5 gene(c.3393_3419del),which resulted in deletion of amino acids 1128-1136(p.G1128_S1136del).It was confirmed as a novel mutation in the pedigree,and the mutation site was not reported in the HGMD.After admission,the patient continued to receive fosinopril sodium treatment to reduce urinary protein secretion and delay renal lesions.After more than half a year of follow-up,the child had no abnormal changes in hearing and eyes,and no abnormal renal function.Conclusion c.3393_3419del mutation of the COL4A5 gene may cause ALPORT syndrome.Early renal patholo-gical examination and genetic testing are of great significance to confirm the diagnosis of ALPORT syndrome,formulate treatment plans,and evaluate prognosis.