Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family
Background: Pathogenic variants in the NPHS2 gene encoding podocin in kidney podocytes are associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) by disrupting podocyte function and the integrity of the glomerular filtration barrier. The outcome is generally poor by progress...
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doaj-bfaf271fb4c64d5eb1e4282adfd715892021-09-23T05:58:07ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602021-09-01910.3389/fped.2021.692727692727Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese FamilyLing Bai0Jing Zhuang1Changrong Zhang2Chen Lu3Xuefei Tian4Hong Jiang5Department of Nephrology and Rheumatology, Children's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDivision of Nephrology, Department of Internal Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDivision of Nephrology, Department of Internal Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaDivision of Nephrology, Department of Internal Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaSection of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, United StatesDivision of Nephrology, Department of Internal Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, ChinaBackground: Pathogenic variants in the NPHS2 gene encoding podocin in kidney podocytes are associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) by disrupting podocyte function and the integrity of the glomerular filtration barrier. The outcome is generally poor by progressing into end-stage kidney disease (ESKD). With the help of gene diagnostics, we can further understand the role of podocin of podocytes in the development and progression of SRNS. However, the pathological mutation of NPHS2 and clinical relevance remain further elusive.Case Presentation: Two siblings, a 15-year-old girl and her 10-year-old younger brother from a consanguineous Chinese family, presented with nephrotic syndrome. Both of them developed progressive proteinuria starting from the 5-year-old of age. The renal pathological lesions for them revealed focal segmental glomerulosclerosis (FSGS). There was no response to the glucocorticoid, calcineurin inhibitors, and rituximab treatment. The female affected patient received the hemodialysis treatment due to ESKD in June 2020; the male patient was still in follow-up presenting with SRNS. The mutational screening of the two patients and their parents using Trio whole-exome sequencing showed the NPHS2 gene de novo missense mutation in exon 5 (A593C), for which the two siblings were homozygous and their parents confirmed heterozygous asymptomatic carriers. No other SRNS-related gene variants with the SRNS were determined.Conclusion: Pathological gene variants screening in children clinically suspected with SRNS might be helpful in the diagnosis as well as appropriate decisions on treatment strategies and prediction of prognosis.https://www.frontiersin.org/articles/10.3389/fped.2021.692727/fullsteroid-resistant nephrotic syndromemutationNPHS2genetic testingfocal segmental glomerulosclerosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ling Bai Jing Zhuang Changrong Zhang Chen Lu Xuefei Tian Hong Jiang |
spellingShingle |
Ling Bai Jing Zhuang Changrong Zhang Chen Lu Xuefei Tian Hong Jiang Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family Frontiers in Pediatrics steroid-resistant nephrotic syndrome mutation NPHS2 genetic testing focal segmental glomerulosclerosis |
author_facet |
Ling Bai Jing Zhuang Changrong Zhang Chen Lu Xuefei Tian Hong Jiang |
author_sort |
Ling Bai |
title |
Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family |
title_short |
Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family |
title_full |
Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family |
title_fullStr |
Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family |
title_full_unstemmed |
Case Report: The Monogenic Familial Steroid-Resistant Nephrotic Syndrome Caused by a Novel Missense Mutation of NPHS2 Gene A593C in a Chinese Family |
title_sort |
case report: the monogenic familial steroid-resistant nephrotic syndrome caused by a novel missense mutation of nphs2 gene a593c in a chinese family |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pediatrics |
issn |
2296-2360 |
publishDate |
2021-09-01 |
description |
Background: Pathogenic variants in the NPHS2 gene encoding podocin in kidney podocytes are associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) by disrupting podocyte function and the integrity of the glomerular filtration barrier. The outcome is generally poor by progressing into end-stage kidney disease (ESKD). With the help of gene diagnostics, we can further understand the role of podocin of podocytes in the development and progression of SRNS. However, the pathological mutation of NPHS2 and clinical relevance remain further elusive.Case Presentation: Two siblings, a 15-year-old girl and her 10-year-old younger brother from a consanguineous Chinese family, presented with nephrotic syndrome. Both of them developed progressive proteinuria starting from the 5-year-old of age. The renal pathological lesions for them revealed focal segmental glomerulosclerosis (FSGS). There was no response to the glucocorticoid, calcineurin inhibitors, and rituximab treatment. The female affected patient received the hemodialysis treatment due to ESKD in June 2020; the male patient was still in follow-up presenting with SRNS. The mutational screening of the two patients and their parents using Trio whole-exome sequencing showed the NPHS2 gene de novo missense mutation in exon 5 (A593C), for which the two siblings were homozygous and their parents confirmed heterozygous asymptomatic carriers. No other SRNS-related gene variants with the SRNS were determined.Conclusion: Pathological gene variants screening in children clinically suspected with SRNS might be helpful in the diagnosis as well as appropriate decisions on treatment strategies and prediction of prognosis. |
topic |
steroid-resistant nephrotic syndrome mutation NPHS2 genetic testing focal segmental glomerulosclerosis |
url |
https://www.frontiersin.org/articles/10.3389/fped.2021.692727/full |
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