CAJ | 학술논문

目的分析1个以蛋白尿为主,伴镜下血尿家系的临床特征,并对可能的致病基因进行筛查.方法调查1个以蛋白尿为主,伴镜下血尿的汉族家系,收集临床资料,绘制家系图谱,并对家系中所有成员进行尿液筛查,并留取其外周血,对尿液筛查异常的一对同胞及其父母进行NPHS1和NPHS2基因所有外显子、WTI基因外显子8和9,以及外显子和内含子交界区直接测序.结果该家系共有3代,17名成员.同一代中发病的有2例,男、女各1例,平均发病年龄1.3岁.临床资料分析显示,该家系临床特点符合常染色体隐性遗传.先证者表现初发型激素耐药肾病综合征,肾脏病理光镜下表现局灶增生性肾小球肾炎,免疫荧光IgA、IgM、C1q和C3均阴性,Ⅳ型胶原蛋白α1、α3和α5链均阳性,电镜下基底膜正常,足突融合.2例患儿在NPHS2基因外显子3和4上均存在杂合p.R138Q(c.413G＞ A)和p.L156FfX11(c.467-468 insT),其中p.R138Q错义突变来自母亲,p.L156FfX11为移码突变来自父亲,2个突变均为报道的致病性突变,前者为NPHS2基因最常见的突变,后者仅在我国人群中报道.结论 p.L156FfX11突变可能是我国肾病综合征儿童的一个特异性突变.NPHS2基因突变不仅可引起蛋白尿,也可伴镜下血尿.NPHS2基因突变引起的肾脏病理不仅可表现为局灶节段性肾小球硬化,还可以为局灶增生性肾小球肾炎,肾脏病理改变可能仅是疾病病程的反映.
목적 분석1개이단백뇨위주,반경하혈뇨가계적림상특정,병대가능적치병기인진행사사.방법 조사1개이단백뇨위주,반경하혈뇨적한족가계,수집림상자료,회제가계도보,병대가계중소유성원진행뇨액사사,병류취기외주혈,대뇨액사사이상적일대동포급기부모진행NPHS1화NPHS2기인소유외현자、WTI기인외현자8화9,이급외현자화내함자교계구직접측서.결과 해가계공유3대,17명성원.동일대중발병적유2례,남、녀각1례,평균발병년령1.3세.림상자료분석현시,해가계림상특점부합상염색체은성유전.선증자표현초발형격소내약신병종합정,신장병리광경하표현국조증생성신소구신염,면역형광IgA、IgM、C1q화C3균음성,Ⅳ형효원단백α1、α3화α5련균양성,전경하기저막정상,족돌융합.2례환인재NPHS2기인외현자3화4상균존재잡합p.R138Q(c.413G＞ A)화p.L156FfX11(c.467-468 insT),기중p.R138Q착의돌변래자모친,p.L156FfX11위이마돌변래자부친,2개돌변균위보도적치병성돌변,전자위NPHS2기인최상견적돌변,후자부재아국인군중보도.결론 p.L156FfX11돌변가능시아국신병종합정인동적일개특이성돌변.NPHS2기인돌변불부가인기단백뇨,야가반경하혈뇨.NPHS2기인돌변인기적신장병리불부가표현위국조절단성신소구경화,환가이위국조증생성신소구신염,신장병리개변가능부시질병병정적반영.
Objective To investigate the clinic features of a family present with proteinuria and microscopic hematuria,and screen 3 commonly pathogenic genes of hereditary proteinuria syndrome.Methods Clinical data of a family present with proteinuria and microscopic hematuria were collected and analyzed.Pedigree of the family was drawn.Urine screening was conducted to all members of the family.Peripheral blood was taken from all members of the family.Direct sequencing of all exons of NPHS1 and NPHS2 gene and exon 8,9 of WT1 gene was performed on 2 patients and their parents.Results The family had 3 generations,17 members.There were 2 sibling patients in the family.One was a female,the other was male.The average age onset was 1.3 years.Analysis of clinical data revealed the family genetic features was consistent with the autosomal recessive inheritance.The proband presented with initial steroid-resistant nephrotic syndrome.His renal pathological changes under light microscope showed focal proliferative glomerulonephritis.Under immunofluorescence microscope IgA,IgM,C1q and C3 were all negative,but type Ⅳ collagen α1,α3 and α5 chains were positive.The basement membrane was normal,and foot process fusion was found under the electron microscope.Two patients both had heterozygous p.R138Q (c.413 G ＞ A) and p.L156FfX11 (c.467-468insT) in the NPHS2 gene exon 3 and 4.Analysis mutation of NPHS2 gene in the family revealed that p.R138Q missense mutation and p.L156FfX11 frameshift mutation were from their parents,respectively.Two mutations had been reported before,which were disease-causing mutation.The former was the most common mutation of NPHS2 gene in European population,but the latter only had been reported in the Chinese population.Conclusions The p.L156FfX11 mutation may be a specific mutation in Chinese children with nephrotic syndrome.Mutations of NPHS2 gene can not only cause proteinuria,but also be associated with microscopic hematuria.Renal pathological changes caused by NPHS2 gene mutation could not only become focal segmental glomerulosclerosis,but also be focal proliferative glomerulonephritis.Renal pathological changes may simply reflect the course of the disease.