CAJ | 학술논문

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IgM＋，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COL4A521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。
목적：인동Alport종합정시도치인동종말기신병적주요질병지일，기진단급치료균유국한성。문중지재대표현위가족성혈뇨병반성유전적신염적가계진행림상급기인연구，이발현기가능적치병기인급치병위점。방법대가계중7위환자진행신천자명학병리류형，신조직급피부Ⅳ형효원염색，외현자측서방법진행기인측서급험증，동시대혈급뇨액진행분석。결과선증자신장병리표현위계막증생성병변，광경결과IgM＋，전경하기막무증후혹변박，면역형광Ⅳ형효원면역형광무결실。선증자COL4A521호외현자발생결실돌변（c．1365＿1373del TCCAGGCCC），교지야생형단백적1685개안기산，돌변형단백부유1682개안기산。차돌변위이지기인신돌변。결론수차보도료일개치Alport 종합정신적결실돌변，대지도가족중녀성환자재생육시，통과산전기인진단혹배태식입전유전학진단기술조단해질병유중요의의。
Objective Alport syndrome is one of the diseases that may lead to the end-stage renal disease ( ESRD) in chil-dren, and the methods for its diagnosis and treatment remain quite limited.This study aimed to investigate the clinical and genetic di-agnosis 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-Ⅳcollagen in the nephridial and skin tissue, conducted gene sequencing i-dentification using the exon sequence method, and examined the blood and urine samples from the patients. Results Renal patholo-gy 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-Ⅳcollagen on immunofluorescence analysis.Mutation of c.1365_1373del TCCAGGCCC (p.Pro456_Pro458del3) 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.