Genetic analysis and outcomes of Omani children with steroid-resistant nephrotic syndrome.
Genetic analysis and outcomes of Omani children with steroid-resistant nephrotic syndrome.
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DOI：
10.1002/mgg3.2201
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发表时间：
2023-09
影响因子：
2
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中科院分区：
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肾病综合征(NS)是儿科肾病医生最常见的肾脏疾病之一，其定义为大量蛋白尿(>；3.5 g/24 h)、低蛋白血症(<；3.5 g/dL)、浮肿和高脂血症。大多数NS儿童对激素敏感，经强的松龙治疗后预后良好。然而，其中10%-20%的人患有激素抵抗型肾病综合征(SRNS)，对治疗无效。这些儿童中有很大一部分进展为肾衰竭。这项回顾性研究旨在确定阿曼13岁以下 儿童中SRNS的潜在遗传原因，时间跨度为15年，包括来自50个不同家庭的77名儿童。我们使用靶向Sanger测序结合下一代测序方法来进行分子诊断。我们发现61例(79.2%)SRNS儿童存在致病基因变异，存在较高的潜在遗传病因。这些基因解决的SRNS患者大多是血缘关系密切的父母所生，其变异处于纯合子状态。NPHS2的致病变异是本研究中37例(48.05%)SRNS的最常见原因。16例患儿也发现NPHS1致病变异，尤其是先天性肾病综合征(CNS)患儿。已确定的其他遗传原因包括LAMB2、PLCE1、MYO1E和NUP93的致病变异。NPHS2和NPHS1基因变异是阿曼儿童SRNS最常见的遗传原因。然而，其他几个SRNS致病基因变异的患者也被发现。我们建议在所有存在这种表型的儿童中筛查所有与SRNS有关的基因，这将有助于临床管理决策和受影响家庭的遗传咨询。肾病综合征是儿科肾病医生最常见的肾脏疾病之一。这项对77名阿曼儿童进行的研究确定了激素抵抗型肾病综合征(SRNS)的潜在遗传原因。在我们的研究中，NPHS2的致病变异是SRNS最常见的原因，几乎在所有病例中都可以看到。我们建议在所有存在这种表型的儿童中筛查所有与SRNS有关的基因，这将有助于临床管理决策和受影响家庭的遗传咨询。
Nephrotic syndrome (NS) is one of the most common kidney disorders seen by pediatric nephrologists and is defined by the presence of heavy proteinuria (>3.5 g/24 h), hypoalbuminemia (<3.5 g/dL), edema, and hyperlipidemia. Most children with NS are steroid‐responsive and have a good prognosis following treatment with prednisolone. However, 10%–20% of them have steroid‐resistant nephrotic syndrome (SRNS) and fail to respond to treatment. A significant proportion of these children progress to kidney failure. This retrospective study aimed to determine the underlying genetic causes of SRNS among Omani children below 13 years old, over a 15‐year period and included 77 children from 50 different families. We used targeted Sanger sequencing combined with next‐generation sequencing approaches to perform molecular diagnostics. We found a high rate of underlying genetic causes of SRNS in 61 (79.2%) children with pathogenic variants in the associated genes. Most of these genetically solved SRNS patients were born to consanguineous parents and variants were in the homozygous state. Pathogenic variants in NPHS2 were the most common cause of SRNS in our study seen in 37 (48.05%) cases. Pathogenic variants in NPHS1 were also seen in 16 cases, especially in infants with congenital nephrotic syndrome (CNS). Other genetic causes identified included pathogenic variants in LAMB2, PLCE1, MYO1E, and NUP93. NPHS2 and NPHS1 genetic variants were the most common inherited causes of SRNS in Omani children. However, patients with variants in several other SRNS causative genes were also identified. We recommend screening for all genes responsible for SRNS in all children who present with this phenotype, which will assist in clinical management decisions and genetic counseling for the affected families. Nephrotic syndrome is one of the most common kidney disorders seen by pediatric nephrologists. This study in 77 Omani children determined the underlying genetic causes of steroid‐resistant nephrotic syndrome (SRNS). Pathogenic variants in NPHS2 were the most common cause of SRNS in our study seen in almost half of all cases. We recommend screening for all genes responsible for SRNS in all children who present with this phenotype, which will assist in clinical management decisions and genetic counseling for the affected families.
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影响因子：
6
作者：
Al Alawi, Intisar;Al Salmi, Issa;Sayer, John A.
通讯作者：
Sayer, John A.
影响因子：
3.9
作者：
Beltcheva, O;Martin, P;Tryggvason, K
通讯作者：
Tryggvason, K
影响因子：
13.2
作者：
Eckardt, Kai-Uwe;Berns, Jeffrey S.;Kasiske, Bertram L.
通讯作者：
Kasiske, Bertram L.
影响因子：
3.5
作者：
Al-Hamed, Mohamed H.;Al-Sabban, Essam;Meyer, Brian F.
通讯作者：
Meyer, Brian F.
DOI：
10.1007/s00467-022-05762-4
发表时间：
2023-05
期刊：
Pediatric nephrology (Berlin, Germany)
影响因子：
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作者：
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