NPHS2 Gene Mutation and Polymorphisms in Indonesian Children with Steroid-Resistant Nephrotic Syndrome

Dedi Rachmadi,Leo Monnens,Ani Melani

doi:10.4236/ojped.2015.51006

Dedi Rachmadi, Leo Monnens + Show 1 more

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https://doi.org/10.4236/ojped.2015.51006

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Abstract

Objective: Although several NPHS2 gene mutations and polymorphisms were described and associated with clinical manifestation of steroid-resistant nephrotic syndrome (SRNS), the occurrence of these genetic abnormalities or variants appeared to be influenced by race and ethnic group. We have investigated probable mutations and variants in NPHS2 gene involved in SRNS and their association with clinical manifestations. Methods: We examined 28 children with primary SRNS whovisited the pediatric nephrology division of 10 teaching hospitals in Indonesia. Molecular genetic studies of the NPHS2 gene were conducted through screenings for the exon 1, exon 2, and exon 8. The mutational analysis of NPHS2 was performed by DNA sequencing. Fisher’s Exact Test was used to determine the correlation between NPHS2 polymorphisms and clinical manifestations.Results: Seven females (25%) and 21 males (75%) participated in the study. The mean age of the subjects with 95% CI is: 7.6 (6.1 - 9.0) years while the mean age at onset of disease with 95% CI is: 5.4 (3.9 - 7.0) years. Sixteen patients (57.14%) were younger than 6 years at the onset of disease. Seventeen (60.7%) subjects had normal eGFR, while 11 (39.3%) had chronic renal insufficiency. The mean eGFR of the subjects with 95% CI is: 111.4 (87.7 - 135.1) ml/min/1.73 m2. The mean systolic blood pressure with 95% CI is: 117.0 (108.9 - 125.1) mmHg and the mean diastolic blood pressure with 95% CI is: 77.0 (70.3 - 83.7) mmHg. We identified 6 NPHS2polymorphisms, i.e. g.-52G>T, c.101A>G, g.-117C>T, c.288C>T, c.954C>T, and c.1038A>G and no mutation was found. There was no correlation between NPHS2 polymorphisms and clinical manifestations (p > 0.05). Conclusion: The results demonstrate no mutation of NPHS2 gene, and the 6 NPHS2 gene polymorphisms that were identified have no correlation with the clinical manifestation in Indonesian children with SRNS.

Highlights

Steroid-resistant nephrotic syndrome (SRNS) is defined as a condition where nephrotic syndrome patients do not achieve remission after a full dose of single drug prednison therapy during the first four weeks [1] [2]
The study population consisted of 59 Indonesian pediatric patients with primary steroid resistant nephrotic syndrome
Subjects were recruited from patients who visited the pediatric nephrology division of 10 education hospitals in several cities in Indonesia, i.e. Bandung, Jakarta, Yogyakarta, Semarang, Surabaya, Denpasar, Medan, Palembang, Makassar, and Manado

Summary

Introduction

Steroid-resistant nephrotic syndrome (SRNS) is defined as a condition where nephrotic syndrome patients do not achieve remission after a full dose of single drug prednison therapy during the first four weeks [1] [2]. About 50 NPHS2 gene mutations and variants and/or nonsilent polymorphisms have been reported and recognized as potentially involved in proteinuria [6]. Information about NPHS2 variants for different racial and ethnic groups are lacking in terms of the variant population frequency and their association with clinical manifestations. In Indonesia, knowledge on NPHS2 mutations and variants in children with SRNS is lacking. We decided to evaluate the presence of probable mutations and variants in NPHS2 gene which are involved in SRNS and their association with clinical manifestations

Methods

Results

Conclusion