新X连锁缺失突变致Alport综合征的研究  

Novel deletion mutation of type-Ⅳ collagen in a Chinese family with Alport syndrome

作　　者：高春林[1] 夏正坤[1] 樊忠民[1] 高远赋[1] 

机构地区：[1]南京军区南京总医院儿科,南京医学博士210002

出　　处：《医学研究生学报》2015年第9期929-933,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81100592;81270800)

摘　　要：目的儿童Alport综合征是导致儿童终末期肾病的主要疾病之一,其诊断及治疗均有局限性。文中旨在对表现为家族性血尿并伴性遗传的肾炎的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。方法对家系中7位患者进行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,同时对血及尿液进行分析。结果先证者肾脏病理表现为系膜增生性病变,光镜结果 Ig M+,电镜下基膜无增厚或变薄,免疫荧光Ⅳ型胶原免疫荧光无缺失。先证者COL4A5 21号外显子发生缺失突变(c.1365_1373del TCCAGGCCC),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。此突变为已知基因新突变。结论首次报道了一个致Alport综合征新的缺失突变,对指导家族中女性患者再生育时,通过产前基因诊断或胚胎植入前遗传学诊断技术阻断该疾病有重要意义。Objective Alport syndrome is one of the diseases that may lead to the end-stage renal disease （ESRD） in children, and the methods for its diagnosis and treatment remain quite limited. This study aimed to investigate the clinical and genetic diagnosis of a Chinese family with hematuria companied by genetic nephritis. Methods We analyzed the renal pathology of 7 patients in a family, performed immunofluorescence staining of type-Ⅳ collagen in the nephridial and skin tissue, conducted gene sequencing identification using the exon sequence method, and examined the blood and urine samples from the patients. Results Renal pathology manifested mesenterium hyperplasia in the index patient, with IgM ＋ under the light microscope, no thickening or thinning under the electromicroscope, and no absence of type-Ⅳ collagen on immunofluorescence analysis. Mutation of c. 1365_1373del TCCAGGCCC （p. Pro456_Pro458de13） was observed in exon 21 of the COL4A5 gene. Only 1682 amino acids were found in the mutated protein as compared with 1685 in the wild type. Conclusion This is the first case of Alport syndrome induced by gene deletion mutation ever reported in China and abroad. There are many female patients in this family, all with a high risk of reproduction failure. Antepartal gene diagnosis or genetic diagnosis before embryo transfer may contribute to the prevention of the disease.

关 键 词：ALPORT综合征 COL4A5基因 儿童 

分 类 号：R692.6[医药卫生—泌尿科学]