scholarly journals Three Novel Mutations in the NPHS1 Gene in Vietnamese Patients with Congenital Nephrotic Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Thi Kim Lien Nguyen ◽  
Van Dem Pham ◽  
Thu Huong Nguyen ◽  
Trung Kien Pham ◽  
Thi Quynh Huong Nguyen ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Missense Mutation ◽  
Mutational Analysis ◽  
Severe Disease ◽  
Congenital Nephrotic Syndrome ◽  
Compound Heterozygous ◽  
Recessive Trait ◽  
Heterozygous Missense Mutation ◽  
Nphs1 Gene ◽  
Heterozygous Variant

Congenital nephrotic syndrome, a rare and severe disease, is inherited as an autosomal recessive trait. The disease manifests shortly after birth and occurs predominantly in families of Finnish origin but has now been observed in all countries and races. Mutations in the NPHS1 gene, which encodes nephrin, are the main causes of congenital nephrotic syndrome in patients. In this study, we report the first mutational analysis of the NPHS1 gene in three unrelated children from three different Vietnamese families. These patients were examined and determined to be suffering from congenital nephrotic syndrome in the Department of Pediatrics, Vietnam National Hospital of Pediatrics. All 29 exons and exon-intron boundaries of NPHS1 were analyzed by PCR and DNA sequencing. Genetic analysis of the NPHS1 gene revealed one compound heterozygous variant p.Glu117Lys, one heterozygous missense mutation p.Asp310Asn, and one heterozygous frame-shifting mutation (c.3250_3251insG causing p.Val1084Glyfs⁎12) in patient 1. In patient 2, one heterozygous variant p.Glu117Lys and one novel heterozygous missense mutation p.Ser324Ala were identified. Finally, a novel missense mutation p.Arg802Leu and a novel nonsense mutation (c.2442C>G causing p.K792⁎) were identified in patient 3.

Novel NPHS1 gene mutations in a Chinese family with congenital nephrotic syndrome

2016 ◽  
Vol 95 (1) ◽  
pp. 161-166 ◽  
Author(s):  
FENGJIE YANG ◽  
YAXIAN CHEN ◽  
YU ZHANG ◽  
LIRU QIU ◽  
YU CHEN ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Gene Mutations ◽  
Congenital Nephrotic Syndrome ◽  
Chinese Family ◽  
Nphs1 Gene

scholarly journals 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?

Medicina ◽  
2019 ◽  
Vol 55 (4) ◽  
pp. 102
Author(s):  
Nguyen Thi Kim Lien ◽  
Pham Van Dem ◽  
Nguyen Thu Huong ◽  
Tran Minh Dien ◽  
Ta Thi Thu Thuy ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Congenital Nephrotic Syndrome ◽  
Disease Status ◽  
Sequencing Data ◽  
Coding Region ◽  
Mild Disease ◽  
Filtration Barrier ◽  
Homozygous Genotype ◽  
Nphs1 Gene ◽  
New Variant

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.

scholarly journals NPHS1 gene mutation in Japanese patients with congenital nephrotic syndrome

2009 ◽  
Vol 24 (8) ◽  
pp. 2411-2414 ◽  
Author(s):  
K. Aya ◽  
J. Shimizu ◽  
Y. Ohtomo ◽  
K. Satomura ◽  
H. Suzuki ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Gene Mutation ◽  
Congenital Nephrotic Syndrome ◽  
Japanese Patients ◽  
Nphs1 Gene

A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome

2012 ◽  
Vol 259 (12) ◽  
pp. 2590-2598 ◽  
Author(s):  
Lubov Blumkin ◽  
Sara Kivity ◽  
Dorit Lev ◽  
Sarit Cohen ◽  
Ruth Shomrat ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Large Deletion ◽  
Compound Heterozygous ◽  
Heterozygous Missense Mutation

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

2020 ◽  
Vol 17 (3) ◽  
pp. 419-425
Author(s):  
Nguyen Thi Kim Lien ◽  
Pham Van Dem ◽  
Nguyen Thu Huong ◽  
Tran Minh Dien ◽  
Nguyen Huy Hoang ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Genetic Counseling ◽  
Glomerular Filtration ◽  
Genetic Disease ◽  
Congenital Nephrotic Syndrome ◽  
Ensembl Database ◽  
Nphs1 Gene ◽  
Pcr Products

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.

scholarly journals Congenital nephrotic syndrome may respond to cyclosporine A: A case report and review of literature

2017 ◽  
Vol 145 (7-8) ◽  
pp. 407-410 ◽  
Author(s):  
Bilsana Mulic ◽  
Gordana Milosevski-Lomic ◽  
Dusan Paripovic ◽  
Divna Kruscic ◽  
Mersudin Mulic ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Cyclosporine A ◽  
Partial Remission ◽  
Enzyme Inhibitor ◽  
Severe Disease ◽  
Congenital Nephrotic Syndrome ◽  
Steroid Resistant ◽  
Steroid Resistant Nephrotic Syndrome ◽  
Long Term Effect ◽  
Intravenous Gamma Globulin

Introduction. Congenital nephrotic syndrome (CNF) is manifested at birth or within the first three months of life. The Finnish-type of CNF is caused by the mutation of the NPHS1 gene, which encodes nephrin in the podocyte slit diaphragm. It is a very severe disease, for which immunosuppressive therapy is not advised. Here we describe a patient with CNF who responded to CsA by partial remission. Case outline. A girl aged 2.5 months presented with severe non-syndromic steroid-resistant nephrotic syndrome. She needed aggressive support including daily albumin infusions and diuretics. Substitution of vitamin D, thyroxin, and anticoagulants were regularly administered. She was also treated with angiotensin converting enzyme inhibitor, without clear benefits regarding proteinuria. In addition, she received intravenous gamma-globulin replacement therapy and antibiotics during frequent infections. While waiting for the results of genetic analyses and faced with many problems related to daily albumin infusions, infections, and thromboembolic complications, cyclosporine A (CsA) was introduced as an alternative to early nephrectomy and consequent renal failure. The patient responded by partial remission and CsA treatment continued at home without the albumin infusions. After almost five years since the beginning of the treatment, the patient?s renal function remains unreduced. Conclusion. Our case demonstrates that CsA can induce partial remission in patients with genetic forms of steroid-resistant nephrotic syndrome without influencing the glomerular filtration rate. However, its long-term effect and safety should carefully be monitored.

scholarly journals Genetic Variations and Clinical Features of NPHS1-Related Nephrotic Syndrome in Chinese Children: A Multicenter, Retrospective Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Liping Rong ◽  
Lizhi Chen ◽  
Jia Rao ◽  
Qian Shen ◽  
Guomin Li ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Clinical Manifestations ◽  
Congenital Nephrotic Syndrome ◽  
Chinese Children ◽  
Compound Heterozygous ◽  
Childhood Onset ◽  
Effective Response ◽  
Registration System ◽  
Novel Variants ◽  
Compound Heterozygous Variants

Introduction: Few studies have addressed the genetic spectrum of NPHS1 variants in Chinese children with nephrotic syndrome. In this multicenter study, the clinical manifestations and features of NPHS1 variants in Chinese children with nephrotic syndrome were researched.Method: Genotypical and phenotypical data from 30 children affected by NPHS1 variants were collected from a multicenter registration system in China and analyzed retrospectively.Results: The patients were divided into two groups: congenital nephrotic syndrome (CNS [n = 24]) and non-CNS (early onset nephrotic syndrome [n = 6]). Renal biopsy was performed on four patients in the non-CNS group, revealing minimal change disease in three and focal segmental glomerulosclerosis in one. A total of 61 NPHS1 variants were detected, involving 25 novel variants. The “recurrent variants” included c.928G>A(p.Asp310Asn) in eight patients with CNS, followed by c.616C>A(p.Pro206Thr) in four, and c.2207T>C (p.Val736Ala) in three. Steroid treatment was applied in 29.2% (7/24)of the patients in the CNS group and 50% (3/6) of the patients in the non-CNS group. One patient in each group experienced complete remission but relapsed subsequently. Immunosuppressants were administered to three patients in the non-CNS group, eliciting an effective response. In the CNS group, three patients underwent renal transplantation and six died mainly from infection.Conclusion: Variants of NPHS1 cause CNS and early childhood-onset nephrotic syndrome. NPHS1 variants in Chinese individuals with nephrotic syndrome (NS) were mainly compound heterozygous variants, and c.928G>A(p.Asp310Asn) in exon 8 may act as a recurrent variant in the Chinese population, followed by c.616C>A(p.Pro206Thr) in exon 6. Steroids and immunosuppressants may be effective in selected patients.

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