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Nucleotide Variations in the NPHS2 Gene in Greek Children with Steroid-Resistant Nephrotic Syndrome

机译:激素抵抗性肾病综合征的希腊儿童NPHS2基因中的核苷酸变异。

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摘要

Mutations in the NPHS2 gene, encoding podocin, are a major cause of autosomal-recessive steroid-resistant nephrotic syndrome (SRNS) in childhood, accounting for up to 30% of sporadic and 20-40% of familial cases. Among 22 Greek children with a clinical diagnosis of SRNS, mutation analysis was performed in all eight NPHS2 gene exons, using denaturing gradient gel electrophoresis and DNA sequencing. The frequency of all nucleotide variations found in patients was also evaluated in 100 unrelated samples (18-30 years) with no known history of nephrotic disease. Three pathogenic genotypes (R138Q/R138Q, R229Q/A295T, and R168H/R168H) accounted for 3/14 (21%) of sporadic patients; the A295T mutation in exon 8 (c.883G>A) is novel and predicted in silico to be pathogenic. Among the familial cases, a single patient was heterozygous for R229Q. Several known polymorphisms were found, including the in cis variants IVS3-46C>T plus IVS3-21C>T, IVS7+7A>G A and exonic variants S96S (c.288C>T), A318A (c.954T>C), and L346L (c.1038A>G), with allele frequencies comparable to those in other populations. A novel substitution (IVS3-17C>T) was found in two related patients, but in no controls. In conclusion, podocin mutations do not appear to be a major cause of SRNS in Greek children, although the study cohort was small. However, NPHS2 gene analysis could still be considered in Greek SRNS patients to support appropriate management. The present study also contributes potentially useful observations for the clinical management of SRNS patients.
机译:编码Podocin的NPHS2基因突变是儿童常染色体隐性激素抵抗性肾病综合征(SRNS)的主要原因,占散发病例的30%,占家族病例的20-40%。在临床诊断为SRNS的22名希腊儿童中,使用变性梯度凝胶电泳和DNA测序对所有8个NPHS2基因外显子进行了突变分析。还对100例无相关肾病史的无关样品(18-30年)进行了评估,确定了患者体内所有核苷酸变异的频率。三种致病基因型(R138Q / R138Q,R229Q / A295T和R168H / R168H)占散发患者的3/14(21%);外显子8(c.883G> A)中的A295T突变是新颖的,并在计算机上预测是致病的。在家族病例中,单个患者的R229Q是杂合的。发现了几种已知的多态性,包括顺式变体IVS3-46C> T加IVS3-21C> T,IVS7 + 7A> GA和外显子变体S96S(c.288C> T),A318A(c.954T> C)和L346L(c.1038A> G),其等位基因频率可与其他人群相比。在两名相关患者中发现了新的替代药物(IVS3-17C> T),但没有对照组。总之,尽管该研究队列很小,但podocin突变似乎并不是希腊儿童SRNS的主要原因。但是,仍可以考虑在希腊SRNS患者中进行NPHS2基因分析以支持适当的治疗。本研究还为SRNS患者的临床管理提供了潜在有用的观察。

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  • 来源
    《Genetic Testing》 |2009年第2期|249-256|共7页
  • 作者单位

    Medical Genetics, 'Aghia Sofia' Children's Hospital, Athens University, Athens, Greece;

    Department of Pediatric Nephrology, 'P. and A. Kyriakou' Children's Hospital, Athens, Greece;

    Medical Genetics, 'Aghia Sofia' Children's Hospital, Athens University, Athens, Greece;

    Medical Genetics, 'Aghia Sofia' Children's Hospital, Athens University, Athens, Greece;

    Medical Genetics, 'Aghia Sofia' Children's Hospital, Athens University, Athens, Greece;

    Department of Pediatric Nephrology, 'P. and A. Kyriakou' Children's Hospital, Athens, Greece;

    Medical Genetics, 'Aghia Sofia' Children's Hospital, Athens University, Athens, Greece;

    Medical Genetics 'Aghia Sofia' Children's Hospital Athens University Athens 11527 Greece;

  • 收录信息 美国《科学引文索引》(SCI);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 入库时间 2022-08-17 13:21:27

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