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Centromere protein I (CENPI) is a candidate gene for X-linked steroid sensitive nephrotic syndrome

Authors :
Basit, Sulman
Al-Edressi, Howaida Mohammed
Sairafi, Mona Hamza
Hashmi, Jamil Amjad
Alharby, Essa
Safar, Ramzia
Ramzan, Khushnooda
Source :
Journal of Nephrology; 20240101, Issue: Preprints p1-7, 7p
Publication Year :
2024

Abstract

Background: Individuals with proteinuria in association with hypoalbuminemia, edema, and hyperlipidemia are considered as having nephrotic syndrome (NS). NS is the most common kidney disease seen in the paediatric age group. NS is usually classified into steroid resistant nephrotic syndrome (SRNS) and steroid sensitive nephrotic syndrome (SSNS). More than 58 genes have been identified as a monogenic cause of SRNS, however, the genetic architecture of childhood SSNS remains poorly understood. Methods: Here in this study, we performed sequencing of 66 NS candidate genes followed by whole genome SNP genotyping and whole exome sequencing in SSNS families with multiple affected individuals. Results: NS candidate genes sequencing did not identify any pathogenic variant in the known genes. Homozygosity mapping based on an autosomal recessive model failed to detect any shared loss of heterozygosity region in the genome. An unbiased and hypothesis-free exome data analysis identified a missense variant (c.383G>A; p.Arg128Gln) in the CENPIgene. Sanger sequencing of both parents, unaffected and affected individuals confirmed an X-linked inheritance pattern of the variant (c.383G>A) with SSNS phenotype. The variant (c.383G>A) is very rare and is potentially damaging. Conclusion: Collectively, these observations suggest that a specific pathogenic link between SSNS development and alteration in CENPI exists. However, human mutations in CENPIcausing SSNS have not been reported hitherto. Identification of genetic defects underlying SSNS will help in understanding the precise aetiology of SSNS and improved management of children with NS.

Details

Language :
English
ISSN :
11218428 and 17246059
Issue :
Preprints
Database :
Supplemental Index
Journal :
Journal of Nephrology
Publication Type :
Periodical
Accession number :
ejs52258034
Full Text :
https://doi.org/10.1007/s40620-019-00692-1