2007 Fiscal Year Final Research Report Summary
Analysis of NPHS1, NPHS2, ACTN4, WT1 and CD2AP in Japanese patients with congenital nephrotic syndrome
| Project/Area Number |
17591111
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
KOICHI Nakanishi Wakayama Medical University, Pediatrics, Senior Lecturer (50336880)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Norishige Wakayama Medical University, 医学部, Professor (10158412)
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| Project Period (FY) |
2005 – 2007
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| Keywords | nephrin / NPHS1 / NPHS2 / ACTN4 / WT1 / CD2AP / podocin / α-Actinin-4 |
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| Research Abstract |
Background. Congenital nephrotic syndrome (CNS) causes significant renal failure, and is classified into two types: (i) Finnish type; and (ii) other, including diffuse mesangial sclerosis. Mutations of NPHS1 and NPHS2, which encode the slit diaphragm components nephrin and podocin, cause CNS and autosomal recessive familial steroid-resistant nephrotic syndrome, respectively. Most patients with Finnish-type CNS in Europe and the United States have NPHS1 mutations. However, NPHS2 mutations have been detected in some cases. Mutations in ACTN4, encoding α-actinin-4, cause an autosomal dominant focal segmental glomerulosclerosis. Α-Actinin-4 stabilizes the podocyte cytoskeleton structure, connecting with actin filaments. WT1 mutations, causing Wilm's tumor, have been demonstrated in some CNS patients with diffuse mesangial sclerosis. CD2-associated protein, CD2AP, is a cytoplasmic binding partner of nephrin. CD2AP-null mice die of massive proteinuria and CD2AP haploinsufficiency leads to glomerular disease in humans. Systematic investigation of genes for CNS in Japan has never been performed.
Methods. To clarify the role of mutations in these five genes, we used PCR and direct sequencing to investigate all exon and exon-intron boundaries for these genes in 15 unrelated CNS patients from regional pediatric kidney disease centers in Japan.
Results. A novel homozygous nonsense mutation of NPHS1, E246X in exon 7, and a novel homozygous deletion mutation of NPHS1, nt2156 (del8) in exon 16 were detected in one patient each. A novel homozygous nonsense mutation of NPHS2, R196X in exon 5, was found in one patient, and the same heterozygous nonsense mutation was detected in another. No ACTN4, WT1 or CD2AP mutations were detected.
Conclusions. These studies demonstrate that mutation of NPHS1 is not a major cause of CNS in Japanese patients, and that mutation of NPHS2 can be responsible for CNS in this population.
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[Presentation] NPHS1, NPHS2, ACTN4, CD2AP and WT1 analysis in Japanese patients with congenital nephrotic syndrome2006
Author(s)
Sako M, Nakanishi K, Togawa H, Shima Y, Hoshii S, Takahashi S, Wada N, Takahashi Y, Kaku Y, Satomura K, Ikeda M, Yoshikawa, N
Organizer
The 2nd Congress of Asian Society for Pediatric Research
Place of Presentation
Yokohama, JAPAN
Year and Date
20060000
Description
「研究成果報告書概要(欧文)」より
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