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?

Nguyen Thi Kim Lien,Nguyen Van Tung,Ta Thi Thu Thuy,Nguyen Thu Huong,Nguyen Huy Hoang,Pham Van Dem,Tran Minh Dien,Nguyen Thi Quynh Huong

doi:10.3390/medicina55040102

Abstract

Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: 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.

Highlights

Congenital nephrotic syndrome (CNS) is a type of kidney disease that is characterized by elevated proteinuria and occurs in the first three months of life [1]
The variants p.Glu117Lys (c.349G>A, in exon 3) and p.Ser607Arg (c.1821C>A, in exon 14) in the NPHS1 gene were found in patient 2
The combination of the two variants p.Ser1105Ser and p.Arg548Leu, in the homozygous form, could be the cause of his severe symptoms. These variants in the heterozygous forms created only a mild phenotype in patient 1, and did not indicate the phenotype in their parents, but in the homozygous form had created a very severe phenotype in patient 2. These results suggested that a variant can become pathogenic when in a homozygous form

Summary

Introduction

Congenital nephrotic syndrome (CNS) is a type of kidney disease that is characterized by elevated proteinuria and occurs in the first three months of life [1]. Mutations in the NPHS1, NPHS2, PLCE1, and WT1 genes have been identified as the cause of the disease [5,6,7,8,9]. Nephrin is a protein of the immunoglobulin (Ig) family It plays an important role in the structure and the selective filtration function of the glomerular slit diaphragm [10,13]. 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.

Methods

Results

Discussion

Conclusion