J Korean Med Sci.  2009 Jan;24(Suppl 1):S210-S214. 10.3346/jkms.2009.24.S1.S210.

Two Korean Infants with Genetically Confirmed Congenital Nephrotic Syndrome of Finnish Type

• Lee BH
• Ahn YH
• Choi HJ
• Kang HK
• Kim SD
• Cho BS
• Moon KC
• Ha IS
• Cheong HI
• Choi Y

• KMID: 1778164
• DOI: http://doi.org/10.3346/jkms.2009.24.S1.S210

Abstract

Congenital nephrotic syndrome is defined as nephrotic syndrome which manifests in utero or during the first 3 months of life. The prototype of congenital nephrotic syndrome is congenital nephrotic syndrome of Finnish type (CNF, OMIM #602716), which is caused by loss-of-function mutations of the nephrin gene (NPHS1). There have been few clinical case reports of CNF in Korea, but none of which was confirmed by genetic study. Here, we report two children with congenital nephrotic syndrome. Genetic analysis of the NPHS1 gene revealed compound heterozygous frame-shifting mutations (c.2156_2163 delTGCACTGC causing p.L719DfsX4 and c.3250_3251insG causing p.V1084GfsX12) in one patient and a missense mutation (c.1381G>A causing p.R460Q) and a nonsense mutation (c.2442C>G causing p.Y814X) in the other patient. The nonsense mutation was novel. The clinical courses of the patients were typical of CNF. This is the first report of genetically confirmed CNF in Korea to date. The early genetic diagnosis of CNF is important for proper clinical management of the patients and precise genetic counseling of the families.

Keyword

Congenital Nephrotic Syndrome; Congenital Nephrotic Syndrome of Finnish Type; NPHS1 Gene; Nephrin; Mutation

MeSH Terms

Base Sequence
Biopsy
Codon, Nonsense
Female
Frameshift Mutation
Humans
Infant
Infant, Newborn
Korea
Male
Membrane Proteins/*genetics
Microscopy, Electron/methods
Molecular Sequence Data
Mutation
Nephrotic Syndrome/*diagnosis/*genetics

Figure

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  Fig. 1 Renal biopsy findings of both patients (A, Case 1; B, Case 2). The glomeruli showed mesangial hypercellularity in both cases, and diffuse increase of mesangial matrix was noted in Case 2. Tubules revealed focal mild atrophy or loss with focal moderate infiltration of mononuclear cells and mild fibrosis in interstitium in both patients (PAS staining. Magnification: ×400).

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  Fig. 2 Electron microscopic findings of the glomerulus in both cases (A, Case 1; B, Case 2). While the glomerular basement membrane (GBM) measured normal in average thickness with relatively smooth inner and outer contours in Case 1, diffuse thinning of GBM (100 µm) was noted in Case 2. No electron-dense deposits were found. Epithelial foot processes exhibited wide effacement (Magnification: ×7,000 [A], ×10,000 [B]).

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  Fig. 3 Results of the NPHS1 gene analysis of both patients. Case 1 has two frame-shifting deletions, c.2155_2162 delCTGCACTG in exon 16 (A) and c.3250_3251insG in exon 24 (B). The former was inherited from mother, and the latter from father (data not shown). Case 2 has c.1381G>A mutation in exon 11 in one allele (C) and c.2242C>G in exon 18 in the other allele (D). The former was inherited from mother, and the latter from father (data not shown).

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