@article{Najafi_Riedhammer_Rad-High_detec_rate-2022,
author = {Najafi, Maryam and Riedhammer, Korbinian M. and Rad, 
          Aboulfazl and Torbati, Paria Najarzadeh and Berutti, 
          Riccardo and Schule, Isabel and Schroda, Sophie and 
          Meitinger, Thomas and Comic, Jasmina and Bojd, Simin Sadeghi 
          and Baranzehi, Tayebeh and Shojaei, Azadeh and Azarfar, 
          Anoush and Khazaei, Mahmood Reza and Kottgen, Anna and 
          Backofen, Rolf and Karimiani, Ehsan Ghayoor and Hoefele, 
          Julia and Schmidts, Miriam},
title = {High detection rate for disease-causing variants in a 
         cohort of 30 {Iranian} pediatric steroid resistant nephrotic 
         syndrome cases},
journal = {Front Pediatr},
year = {2022},
doi = {10.3389/fped.2022.974840},
volume = {10},
user = {backofen},
pmid = {36245711},
pages = {974840},
number = {},
issn = {2296-2360},
abstract = {BACKGROUND: Steroid resistant nephrotic syndrome (SRNS) 
            represents a significant renal disease burden in childhood 
            and adolescence. In contrast to steroid sensitive nephrotic 
            syndrome (SSNS), renal outcomes are significantly poorer in 
            SRNS. Over the past decade, extensive genetic heterogeneity 
            has become evident while disease-causing variants are still 
            only identified in 30% of cases in previously reported 
            studies with proportion and type of variants identified 
            differing depending on the age of onset and ethnical 
            background of probands. A genetic diagnosis however can have 
            implications regarding clinical management, including kidney 
            transplantation, extrarenal disease manifestations, and, in 
            some cases, even causal therapy. Genetic diagnostics 
            therefore play an important role for the clinical care of 
            SRNS affected individuals. METHODOLOGY AND RESULTS: Here, we 
            performed NPHS2 Sanger sequencing and subsequent exome 
            sequencing in 30 consanguineous Iranian families with a 
            child affected by SRNS with a mean age of onset of 16 
            months. We identified disease-causing variants and one 
            variant of uncertain significance in 22 families (73%), 
            including variants in NPHS1 (30%), followed by NPHS2 (20%), 
            WT1 (7%) as well as in NUP205, COQ6, ARHGDIA, SGPL1, and 
            NPHP1 in single cases. Eight of these variants have not 
            previously been reported as disease-causing, including four 
            NPHS1 variants and one variant in NPHS2, ARHGDIA, SGPL1, and 
            NPHP1 each. CONCLUSION: In line with previous studies in 
            non-Iranian subjects, we most frequently identified 
            disease-causing variants in NPHS1 and NPHS2. While Sanger 
            sequencing of NPHS2 can be considered as first diagnostic 
            step in non-congenital cases, the genetic heterogeneity 
            underlying SRNS renders next-generation sequencing based 
            diagnostics as the most efficient genetic screening method. 
            In accordance with the mainly autosomal recessive 
            inheritance pattern, diagnostic yield can be significantly 
            higher in consanguineous than in outbred populations.}
}