Human Genetics and Genome Research Division, Clinical Genetics Department, National Research Centre, Cairo, Egypt.
Medical Molecular Genetics Department and Genome Research Division, National Research Centre, Cairo, Egypt.
J Formos Med Assoc. 2018 Jan;117(1):48-53. doi: 10.1016/j.jfma.2017.02.012. Epub 2017 Apr 3.
BACKGROUND/PURPOSE: Nephrotic syndrome is the commonest etiology of proteinuria in children. Steroid-resistant nephrotic syndrome (SRNS) is defined by resistance to standard steroid therapy, and it continues to be one of the most intractable etiologies of renal failure. Molecular studies discovered specialized molecules in podocytes that play a role in proteinuria. Mutations in NPHS2 that encodes for podocin constitute a frequent cause of SRNS worldwide. This study aimed to screen for podocin mutations in SRNS Egyptian children and their parents.
Our study included patients from 10 unrelated Egyptian families diagnosed with SRNS. Mutational analysis of the NPHS2 gene was performed by polymerase chain reaction amplification of the whole coding region of the gene and direct sequencing.
Positive consanguinity was detected in five cases, and four of them had a positive family history of SRNS in a family member. Mutational analysis of NPHS2 revealed pathogenic mutations in four cases (40%) including a novel missense in one patient (c.1A>T; p.M1L).
Our study concludes that mutations of NPHS2 gene are common among Egyptian children with SRNS. We support a model where ethnicity plays an important role in specific NPHS2 mutations, since a novel mutation was found in one patient in this study. Future study on a large number of Egyptian patients with SRNS is warranted to identify the actual genetic contribution of this gene in the development of SRNS in our population, which might help in patients' prognosis and management.
背景/目的：肾病综合征是儿童蛋白尿最常见的病因。激素耐药性肾病综合征（SRNS）定义为对标准激素治疗耐药，它仍然是肾衰竭最棘手的病因之一。分子研究发现足细胞中存在专门的分子，这些分子在蛋白尿中起作用。编码足细胞蛋白的 NPHS2 突变构成了全球范围内 SRNS 的常见病因。本研究旨在筛选埃及 SRNS 儿童及其父母的足细胞蛋白基因突变。
我们的研究纳入了 10 个无关埃及家庭的患者，这些家庭的患者被诊断为 SRNS。通过聚合酶链反应扩增基因的整个编码区并直接测序，对 NPHS2 基因进行突变分析。
在五个病例中检测到阳性近亲结婚，其中四个病例在一个家族成员中具有 SRNS 的阳性家族史。NPHS2 的突变分析显示四个病例（40%）存在致病性突变，包括一个新的错义突变（c.1A>T；p.M1L）。
我们的研究表明，NPHS2 基因突变在埃及 SRNS 儿童中很常见。我们支持一种观点，即种族在特定的 NPHS2 突变中起重要作用，因为在本研究的一名患者中发现了一种新的突变。需要对大量埃及 SRNS 患者进行研究，以确定该基因在我们人群中 SRNS 发展中的实际遗传贡献，这可能有助于患者的预后和管理。
