Child ; Diagnosis, Differential ; Humans ; Kidney Diseases ; diagnosis ; genetics ; therapy ; Nephrotic Syndrome ; diagnosis ; therapy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis for a fetus suspected for congenital nephrotic syndrome of Finland (CNF). METHODS: Genomic DNA was extracted from peripheral and umbilical cord blood samples derived from both parents and the fetus. Potential variants were detected by using next-generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The fetus was found to carry compound heterozygous variants c.1440+1G>A and c.925G>T of the NPHS1 gene, which were respectively inherited from its mother and father. CONCLUSION Identification of the compound heterozygous NPHS1 variants has enabled diagnosis of CNF in the fetus and genetic counseling for the affected family.
Female ; Fetus ; Finland ; Heterozygote ; Humans ; Membrane Proteins ; genetics ; Nephrotic Syndrome ; congenital ; diagnosis ; Pregnancy ; Prenatal Diagnosis

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.
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

Adolescent ; Child ; DNA Mutational Analysis ; Genetic Testing ; methods ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Mutation ; Nephrotic Syndrome ; congenital ; diagnosis ; genetics ; Phenotype ; Polymerase Chain Reaction

Alkyl and Aryl Transferases ; genetics ; Child ; DNA, Mitochondrial ; genetics ; Fibroblasts ; metabolism ; Glomerulosclerosis, Focal Segmental ; diagnosis ; drug therapy ; genetics ; Humans ; Kidney Diseases ; diagnosis ; drug therapy ; genetics ; Mitochondrial Diseases ; diagnosis ; drug therapy ; genetics ; Mutation ; Nephrotic Syndrome ; diagnosis ; drug therapy ; genetics ; Protein Kinases ; genetics ; Ubiquinone ; analogs & derivatives ; biosynthesis ; deficiency ; therapeutic use

OBJECTIVETo explore the correlation between Chinese medicine (CM) syndromes and the NPHS1 gene and NPHS2 gene polymorphism as well as corticosteroid sensitivity in patients with minimal change disease (MCD).

METHODSA total of 94 MCD patients were recruited, including 58 steroid-sensitive nephritic syndrome (SSNS) patients and 36 steroid-resistant nephritic syndrome (SRNS) patients. Genomic DNA was obtained from peripheral blood lymphocytes and sequence analysis of single nucleotide polymorphisms (SNPs) in the genes was performed.

RESULTS(1) The SNPs of G349A-3 in NPHS1 gene was found in MCD, but the SNPs of G686A-5 and C695T-5 in NPHS2 gene were not discovered in MCD. (2) When comparing the frequency of genotype AA and allele A in NPHS1 gene (G349A-3), genotype AA and allele A were higher in the SRNS group than in the SSNS group (P < 0.05). (3) When compared with the SRNS group, qi yang deficiency syndrome had a higher incidence in the SSNS group, and yin deficiency syndrome and qi-yin deficiency syndrome had a less incidence in the SSNS, but with no statistical difference (P > 0.05). The rheumatism syndrome had a higher incidence in the SSNS group (P < 0.05). The blood stasis syndrome had a lower incidence in the SSNS with statistical difference (P < 0.05). (4) There was no statistical difference in the correlation between GG, AA, GA and CM syndromes (P > 0.05).

CONCLUSIONSHomozygous mutations of AA and allele A in NPHS1 gene were correlated to SRNS patients of MCD. Rheumatism syndrome patients were prone to be sensitive to corticosteroids, while patients of blood stasis syndrome were prone to be insensitive to corticosteroids. We didn't discover the correlation between NPHS1 gene polymorphism and CM syndrome distribution.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Female ; Genotype ; Homozygote ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Medicine, Chinese Traditional ; Membrane Proteins ; genetics ; Middle Aged ; Nephrosis, Lipoid ; diagnosis ; genetics ; Nephrotic Syndrome ; congenital ; genetics ; Polymorphism, Single Nucleotide ; Yang Deficiency ; Yin Deficiency ; Young Adult