2004 Fiscal Year Final Research Report Summary
Analysis of NPHS1, NPHS2, ACTN4 and WT1 in Japanese patients with congenital nephrotic syndrome
| Project/Area Number |
14570763
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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 |
NAKANISHI Koichi Wakayama Medical University, Medicine, Assistant Professor, 医学部, 助手 (50336880)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Norishige Wakayama Medical University, Professor, 教授 (10158412)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Congenital nephrotic syndrome / NPHS1 / NPHS2 / ACTN4 / WT1 / nephrin / 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. Systematic investigation of genes for CNS in Japan has never been performed.
Methods. To clarify the role of mutations in these four genes, we used PCR and direct sequencing to investigate all exons and exon-intron boundaries for these genes in 13 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 or WT1 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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Research Products
(6 results)
