Abstract
The aim of this study is to screen for variants in NPHS1 and NPHS2, in a cohort of Egyptian children with steroid-resistant nephrotic syndrome (SRNS)/focal segmental glomerulosclerosis (FSGS) and compare the prevalence of such variants among other ethnic groups. The study included 25 patients: 21 children diagnosed clinically as steroid-resistant nephrotic syndrome and confirmed as FSGS by renal biopsy and four patients diagnosed as congenital nephrotic syndrome with FSGS. Mutational analysis revealed nine NPHS2 and NPHS1 variants in 13/25 patients with a pathogenic variant detection rate of 52%. NPHS2 variants were found in 8 patients (32%) while five patients from four unrelated families (20%) harbored variants in NPHS1 gene. Six variants were not described before including a likely founder NPHS2 variant in our population, c.596dupA (p.Asn199LysfsTer14). In conclusion, we reported the largest series of patients with SRNS/FSGS from Egypt and identified many novel NPHS1 and NPHS2 variants expanding their mutational spectrum. Further studies on a larger number of patients could provide new insights into the pathogenic mechanisms of SRNS/FSGS which might help in patient’s management and prognosis.
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All authors contributed to the study’s conception and design. Material preparation, data collection and analysis were performed by MMT, HMA, OEB, SHED and AR. Methodology was performed by MSAH. The first draft of the manuscript was written by MMT. Writing—review and editing: MMT, HMA and MSAH. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Thomas, M.M., Ahmed, H.M., El-Dessouky, S.H. et al. Spectrum of NPHS1 and NPHS2 variants in egyptian children with focal segmental glomerular sclerosis: identification of six novel variants and founder effect. Mol Genet Genomics 297, 689–698 (2022). https://doi.org/10.1007/s00438-022-01877-3
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DOI: https://doi.org/10.1007/s00438-022-01877-3