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Abstract：
BACKGROUND: Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare disease, accounting for 3-5% of all cases of primary nephritic syndrome. We report an uncommon case of familial MPGN type I associated with a new mutation in the complement factor H gene (CFH).
METHODS: Clinical data were collected on three siblings with known factor H deficiency who presented with MPGN. All underwent immunological and genetic assays. Their parents and ten healthy adults served as controls for the DNA analysis.
RESULTS: All three children presented with recurrent episodes of hematuria and proteinuria, the youngest starting at age 5 months. One child currently has nephrotic syndrome and end-stage renal disease. All of the children were found to be homozygous for a C.262C > A (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a quantitative/functional deficiency of factor H. The parents of the three siblings were found to be heterozygous for the mutation. None of the controls carried this mutation.
CONCLUSIONS: Different mutations in CFH may be responsible for different glomerular diseases, including MPGN type I. A modifier gene or an environmental trigger may contribute to this phenotype-genotype discrepancy. Understanding the role of the alternative complement pathway in this disease would allow us to offer these patients more targeted therapy, including a clinical trial of eculizumab.
METHODS: Clinical data were collected on three siblings with known factor H deficiency who presented with MPGN. All underwent immunological and genetic assays. Their parents and ten healthy adults served as controls for the DNA analysis.
RESULTS: All three children presented with recurrent episodes of hematuria and proteinuria, the youngest starting at age 5 months. One child currently has nephrotic syndrome and end-stage renal disease. All of the children were found to be homozygous for a C.262C > A (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a quantitative/functional deficiency of factor H. The parents of the three siblings were found to be heterozygous for the mutation. None of the controls carried this mutation.
CONCLUSIONS: Different mutations in CFH may be responsible for different glomerular diseases, including MPGN type I. A modifier gene or an environmental trigger may contribute to this phenotype-genotype discrepancy. Understanding the role of the alternative complement pathway in this disease would allow us to offer these patients more targeted therapy, including a clinical trial of eculizumab.
摘要：
背景：特发性膜增生性肾小球肾炎（MPGN）是一种罕见疾病，占所有原发性肾病综合征病例的3-5%。我们报道了一个罕见的家族性MPGNI型与补体因子H基因（CFH）的新突变相关的病例。
方法：收集了3名已知H因子缺乏且表现为MPGN的兄弟姐妹的临床数据。全部进行了免疫学和遗传学测定。他们的父母和10名健康成年人作为DNA分析的对照。
结果：3名患儿均出现血尿和蛋白尿反复发作，最小的从5个月大开始。一名儿童目前患有肾病综合征和终末期肾病。所有的孩子都被发现是纯合的C.262C>A（p。CFH外显子3中的Pro88Thr）突变，与因子H的定量/功能缺陷有关。发现三个兄弟姐妹的父母对该突变是杂合的。没有一个对照携带这种突变。
结论：CFH的不同突变可能导致不同的肾小球疾病，修饰基因或环境触发因素可能导致这种表型-基因型差异。了解替代补体途径在这种疾病中的作用将使我们能够为这些患者提供更有针对性的治疗，包括依库珠单抗的临床试验。
方法：收集了3名已知H因子缺乏且表现为MPGN的兄弟姐妹的临床数据。全部进行了免疫学和遗传学测定。他们的父母和10名健康成年人作为DNA分析的对照。
结果：3名患儿均出现血尿和蛋白尿反复发作，最小的从5个月大开始。一名儿童目前患有肾病综合征和终末期肾病。所有的孩子都被发现是纯合的C.262C>A（p。CFH外显子3中的Pro88Thr）突变，与因子H的定量/功能缺陷有关。发现三个兄弟姐妹的父母对该突变是杂合的。没有一个对照携带这种突变。
结论：CFH的不同突变可能导致不同的肾小球疾病，修饰基因或环境触发因素可能导致这种表型-基因型差异。了解替代补体途径在这种疾病中的作用将使我们能够为这些患者提供更有针对性的治疗，包括依库珠单抗的临床试验。
