A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan
A spectrum of novel NPHS1 and NPHS2 gene mutations in pediatric nephrotic syndrome patients from Pakistan
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DOI：
10.1016/j.gene.2012.04.063
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发表时间：
2012-07-10
期刊：
影响因子：
3.5
通讯作者：
Mehdi, Syed Qasim
中科院分区：
文献类型：
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作者：
Abid, Aiysha;Khaliq, Shagufta;Mehdi, Syed Qasim
背景：NPHS1和NPHS2基因突变分别是早发性肾病综合征和家族性激素耐药肾病综合征的主要原因之一。方法：对145例肾病综合征(NS)患儿的NPHS1和NPHS2基因进行直接测序分析。该队列包括来自30个家系的36例先天性或婴儿期NS病例和39例家族性病例。结果：共发现NPHS1基因7个纯合子突变(6个新发现)和NPHS2基因4个纯合子突变。所有NPHS1基因突变均发生在早发病例中。在这些患者中，有一名患者有NS家族史。在2例儿童期起病的儿童中发现NPHS2基因的p.R229Q纯合子突变。结论：NPHS1的致病突变发生率较低(22%为早发)。与欧洲人群相比，巴基斯坦NS儿童中的NPHS2(3.3%早发和3.4%)基因的总比例为5.5%。与欧洲家族性SRNS中NPHS2基因突变的高频率相反，巴基斯坦家族性病例中未发现突变。据我们所知，这是首次对南亚散发性和家族性NS病例进行NPHS1和NPHS2基因突变的全面筛查。(C)2012爱思唯尔B.V.保留所有权利。
Background: Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients.Methods: Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families.Results: A total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS.Conclusions: Our results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset. 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NS children as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia. (C) 2012 Elsevier B.V. All rights reserved.