ABSTRACT
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.
ABSTRACT
Objective To elucidate the mutations of NPHS1 gene in children with sporadic steroid-resistant nephrotic syndrome (SRNS) in Southern Chinese Han ethnic group.Methods Peripheral blood samples were collected for genetic analysis from 40 patients with sporadic SRNS and 50 healthy volunteers as control.Genomic DNA was isolated from peripheral blood leucocytes.Twenty-nine exons and exon-intron boundaries of the NPHS1 gene were amplified by polymerase chain reaction.Mutational analysis was performed by DNA sequencing directly.Results Seven variants,928G＞A(D310N),2677A＞G (T893A),2869G＞C (V957L),IVS8+30C＞T,IVS21+14G＞A,IVS25-23C＞T and *142T＞C,of NPHS1 gene were found in 6 of 40 children with sporadic SRNS,whereas they were not found in 50 healthy controls.2677A ＞G,IVS8 +30C ＞T,IVS21 +14G＞A,IVS25-23C ＞T and *142T＞C were novel.Moreover,thirteen already reported NPHS1 polymorphisms,294C＞T,349G＞A,IVS3+15C＞T,IVS3+61A＞G,803G＞A,IVS8+68A＞G,1339G ＞A,1802G ＞C,2223C ＞T,2289C ＞T,IVS24 +36C ＞T,3315G＞A and IVS27 +45C ＞T,were detected in some patients and controls. Conclusions NPHS1 mutations in 6 of 40 children with sporadic SRNS in Southern Chinese Han ethnic group (15％) are detected.NPHS1 mutations are existed in Southern Chinese children,so it is necessary to perform the mutation analysis of NPHS1 gene in those children patients.
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.