A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families
A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families
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DOI：
10.1038/jhg.2013.27
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发表时间：
2013-07-01
影响因子：
3.5
通讯作者：
Meyer, Brian F.
中科院分区：
文献类型：
--
作者：
Al-Hamed, Mohamed H.;Al-Sabban, Essam;Meyer, Brian F.
肾病综合征（NS）是一种以大量蛋白尿、低蛋白血症、水肿和高脂血症为特征的肾脏疾病。在出生后的前3个月内或在多个家庭成员中出现，表明有潜在的遗传原因。为了确定遗传性NS的频率，对来自沙特阿拉伯的62个病例（代表49个NS家族）进行了NPHS1、NPHS2、LAMB2、PLCE 1、CD2AP、MYO1E、WT1、PTPRO和Nei内切核酸酶VIII样1（NEIL 1）突变的筛查。我们在49个研究的家庭中的25个（51%）中检测到可能的致病突变。我们发现，在我们的队列中，NS最常见的遗传原因是NPHS2基因的纯合突变，在49个家族中有11个（22%）。NPHS1和PLCE1基因突变分别允许12%和8%的家庭进行分子遗传学诊断。我们在三个家庭（6%）中检测到新的MYO1E突变。在WT1、PTPRO和NEIL 1中未发现突变。通过计算机模拟试验和种族匹配对照人群的遗传筛查分析了新变体的致病性。这是第一份描述阿拉伯半岛NS分子遗传学的报告。
Nephrotic syndrome (NS) is a renal disease characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. Its presentation within the first 3 months of life or in multiple family members suggests an underlying inherited cause. To determine the frequency of inherited NS, 62 cases (representing 49 families with NS) from Saudi Arabia were screened for mutations in NPHS1, NPHS2, LAMB2, PLCE1, CD2AP, MYO1E, WT1, PTPRO and Nei endonuclease VIII-like 1 (NEIL1). We detected likely causative mutations in 25 out of 49 families studied (51%). We found that the most common genetic cause of NS in our cohort was a homozygous mutation in the NPHS2 gene, found in 11 of the 49 families (22%). Mutations in the NPHS1 and PLCE1 genes allowed a molecular genetic diagnosis in 12% and 8% of families, respectively. We detected novel MYO1E mutations in three families (6%). No mutations were found in WT1, PTPRO or NEIL1. The pathogenicity of novel variants was analyzed by in silico tests and by genetic screening of ethnically matched control populations. This is the first report describing the molecular genetics of NS in the Arabian Peninsula.