Mutations in NPHS1 and PLCE1 (NPHS3) in two Vietnamese patients with conginetal nephrotic syndrome

Congenital nephrotic syndrome (CNS), a genetic disease caused by the mutations in genes on autosomes,is usually occurs in the first three months after birth. The mutations in genes that encode for the structural andfunctional proteins of podocytes lead to loss of the function of glomerular filtration. So far, a number of genesrelated to the disease have been identified such as: NPHS1, NPHS2, PLCE1 (NPHS3), ACTN4, CD2AP, INF2and WT1. In this article, we amplified all of exons in NPHS1 and PLCE1 genes of two Vietnamese patientswith CNS and members of patients’ family. PCR products were purified and sequenced directly on automaticsequencer ABI 3500 Bio System (USA). The sequencing results were compared with the sequences of NPHS1and PLCE1 genes published in the Ensembl database (ENSG00000161270 and ENSG00000138193,respectively) by using BioEdit software to detect mutations. We identified two mutations: c.2398C>T(p.Arg800Cys, exon 18), c.3315A>G (p.Ser1105Ser, exon 26) in NPHS1 gene and two mutations: c.5330 C>T(p.Thr1777Ile, exon 23), c.5780A>G (p.His1927Arg, exon 25) in PLCE1 gene in study patients. These twopatients carried simultaneously the mutations in the NPHS1 and PLCE1 genes with serious phenotype. Theresults of our study might be evidences for the role of mutations in NPHS1 and PLCE1 genes in thedevelopment of disease in patients. These are useful information in identifying the cause of disease and providethe genetic counseling to the patients’ family.

The Role of p.Ser1105Ser (in NPHS1 Gene) and p.Arg548Leu (in PLCE1 Gene) with Disease Status of Vietnamese Patients with Congenital Nephrotic Syndrome: Benign or Pathogenic?

Congenital nephrotic syndrome (CNS), a genetic disease caused by mutations in genes on autosomes, usually occurs in the first three months after birth. A number of genetic mutations in genes, which encode for the components of the glomerular filtration barrier have been identified. We investigated mutations in NPHS1, NPHS2, PLCE1 (NPHS3), and WT1 genes that relate to the disease in Vietnamese patients. We performed genetic analysis of two unrelated patients, who were diagnosed with CNS in the Vietnam National Children’s Hospital with different disease status. The entire coding region and adjacent splice sites of these genes were amplified and sequenced using the Sanger method. The sequencing data were analyzed and compared with the NPHS1, NPHS2, PLCE1, and WT1 gene sequences published in Ensembl (ENSG00000161270, ENSG00000116218, ENSG00000138193, and ENSG00000184937, respectively) using BioEdit software to detect mutations. We detected a new variant p.Ser607Arg and two other (p.Glu117Lys and p.Ser1105Ser) in the NPHS1 gene, as well as two variants (p.Arg548Leu, p.Pro1575Arg) in the PLCE1 gene. No mutations were detected in the NPHS2 and WT1 genes. Patient 1, who presented a heterozygous genotype of p.Ser1105Ser and p.Arg548Leu had a mild disease status but patient 2, who presented a homozygous genotype of these alleles, had a severe phenotype. These results suggest that variants p.Ser1105Ser (in NPHS1 gene) and p.Arg548Leu (in PLCE1 gene) in the homozygous form might play a role in the development of the disease in patients.