CAJ | 학술논문

目的了解儿童Alport综合征(AS)临床表型及基因突变的特点.方法回顾性分析2011年5月至2014年5月于上海交通大学附属儿童医院肾脏风湿科明确诊断并具有完整资料(临床、肾组织病理、基因检测结果)的AS患儿25例.采用外显子捕获-二代测序技术进行基因检测,包括COL4A3、COL4A4、COL4A5基因,并同时进行家系验证.结果 (1)25例患儿中X连锁AS(XL-AS)19例(76％),常染色体隐性遗传AS (AR-AS)6例(24％).25例患儿均以血尿和(或)蛋白尿起病,8例以上呼吸道感染为诱因.其中2例(8％)存在听力损伤,1例(4％)患儿存在眼部病变.(2)25例均行肾组织活检,光镜表现为:16例轻微病变,8例系膜增生,1例局灶节段硬化.电镜下仅2例(8％)见肾小球基底膜致密层撕裂分层等典型AS改变,另4例表现为薄基底膜病,8例系膜增生性改变,6例轻微病变,5例未见肾小球.肾组织Ⅳ型胶原α链间接免疫荧光检测中21例(84％)存在表达缺失.(3)对25例(来自23个家系)行COL4A3、COL4A4及COL4A5基因突变检查,发现突变类型24种(16种突变未见报道).其中COL4A3基因突变1种(4％),COL4A4基因突变5种(21％),COL4A5基因突变18种(75％).同时对25例患儿的直系家庭成员全部可疑致病突变进行了验证,结果发现13例突变遗传自母亲,3例遗传自父亲,2例(同胞姐妹)患儿的1种突变遗传自父亲、另一种遗传自母亲,7例为新生突变.结论 (1)AS以X连锁显性遗传为主,病理检查多表现为轻微病变或系膜增生性改变,电镜下少数患儿可表现为薄基底膜病.(2)25例患儿共检出24种COL4A3、COL4A4、COL4A5基因突变,其中16种未见报道.
목적 료해인동Alport종합정(AS)림상표형급기인돌변적특점.방법 회고성분석2011년5월지2014년5월우상해교통대학부속인동의원신장풍습과명학진단병구유완정자료(림상、신조직병리、기인검측결과)적AS환인25례.채용외현자포획-이대측서기술진행기인검측,포괄COL4A3、COL4A4、COL4A5기인,병동시진행가계험증.결과 (1)25례환인중X련쇄AS(XL-AS)19례(76％),상염색체은성유전AS (AR-AS)6례(24％).25례환인균이혈뇨화(혹)단백뇨기병,8례이상호흡도감염위유인.기중2례(8％)존재은력손상,1례(4％)환인존재안부병변.(2)25례균행신조직활검,광경표현위:16례경미병변,8례계막증생,1례국조절단경화.전경하부2례(8％)견신소구기저막치밀층시렬분층등전형AS개변,령4례표현위박기저막병,8례계막증생성개변,6례경미병변,5례미견신소구.신조직Ⅳ형효원α련간접면역형광검측중21례(84％)존재표체결실.(3)대25례(래자23개가계)행COL4A3、COL4A4급COL4A5기인돌변검사,발현돌변류형24충(16충돌변미견보도).기중COL4A3기인돌변1충(4％),COL4A4기인돌변5충(21％),COL4A5기인돌변18충(75％).동시대25례환인적직계가정성원전부가의치병돌변진행료험증,결과발현13례돌변유전자모친,3례유전자부친,2례(동포저매)환인적1충돌변유전자부친、령일충유전자모친,7례위신생돌변.결론 (1)AS이X련쇄현성유전위주,병리검사다표현위경미병변혹계막증생성개변,전경하소수환인가표현위박기저막병.(2)25례환인공검출24충COL4A3、COL4A4、COL4A5기인돌변,기중16충미견보도.
Objective To analyze the clinical features and gene mutation of Chinese children with Alport syndrome (AS).Method From May 2011 to May 2014,clinical and pathological information gathered from 25 patients was retrospectively analyzed.COL4A5,COL4A4 and COL4A3 genes were analyzed using next-generation sequencing in these patients,and gene mutations of related family members were identified by Sanger method.Result Of these 25 cases,19(76％) had X-linked Alport syndromes (XL-AS),6 had autosomal recessive Alport syndromes (AR-AS).Twenty five patients had an onset of hematuria and proteinuria and in 8 cases the disease was induced by upper respiratory tract infections.Hearing loss was present in 2 of 25 (8％) cases and ocular lesions in 1 of 25 (4％).Renal pathology showed that 16 of them had minimal change disease (MCD),8 mesangial proliferative glomerulonephritis (MsPNG),1 focal segmental glomerulo-sclerosis (FSGS).Extensive lamination and split of glomerular basement membrane (GBM) dense layers were found in 2 (8％) of 25 patients.Twenty one of 25 patients (84％) showed abnormal renal α-chain distribution.COL4A5,COL4A4 and COL4A3 genes of 25 patients (23 families) were analyzed and 24 pathogenic mutations were identified:18 in COL4AS,1 in COL4A3 and 5 in COL4A4.It was observed that 13 patients inherited the mutation from the mother,3 patients inherited from the father,2 patients inherited 1 mutation from the mother and another mutation from the father,and 7 patients carried the novel mutations.Conclusion XL is the main inherited type in AS.Most of patients showed MCD and MsPNG in renal biopsy.This research examined 24 mutations and 16 mutations were not reported previously.