Short Communication Mutations in NPHS2 (podocin) in Mexican children with nephrotic syndrome who respond to standard steroid treatment

Abstract

ABSTRACT. Human nephrotic syndrome has been related to mutations in glomerular proteins. Mutations in the NPHS2 gene that encodes podocin have been described as responsible for steroidresistant nephrotic syndrome. It has been advised to test for NPHS2 mutations in parallel or before giving steroid treatment in nephrotic syndrome patients in order to avoid unnecessary therapy. We identified NPHS2 mutations in Mexican children with nephrotic syndrome. The study included 13 children with nephrotic syndrome and 2 healthy control individuals; 8 patients were steroid-resistant and 5 were steroidsensitive. We analyzed the 3rd exon of NPHS2 by DNA sequencing. Podocin heterozygous missense mutations L139R and L142P were found; the former was found in both steroid-sensitive and steroid- Podocin mutations in nephrotic Mexican children resistant children, while the latter was found in a steroid-resistant child. We conclude that NPHS2 mutations should be investigated to help decide the course of treatment in nephrotic syndrome patients.

NPHS2Mutations: A Closer Look to Latin American Countries

“…Thirty-nine variants, among them 25 missenses, four nonsenses, three splice-sites, four frameshifts, and three in the promoter region were published from June 2013 to February 2017 in a total of 109 out of 829 SRNS patients in many countries: China (Wang et al, 2017) [28]; India (Jaffer et al, 2014; Dhandapani et al 2017; Ramanathan et al 2017) [29–31]; Italy (Benetti et al, 2013) [32]; Iran (Basiratnia et al, 2013) [33]; United Kingdom (Jain et al, 2014) [34]; United States of America (Laurin et al, 2014; Phelan et al, 2015) [35, 36]; Poland (Kuleta et al, 2014) [37]; Finland (Suvanto et al, 2016) [38]; Saudi Arabi (Kari et al, 2013) [39]; Japan (Ogino et al, 2015) [40]; Mexico (Carrasco-Miranda et al, 2013) [41]; Chile (Azocar et al, 2016) [42]; and Brazil (Guaragna et al, 2015) [43]. Ten out of those 39 mutations were unique and had not been annotated in public HGMD (http://www.hgmd.cf.ac.uk/ac/index.php) or in GnomeAD Browser (http://gnomad.broadinstitute.org) or in the Leiden Open Variation Database (https://www.lovd.nl/NPHS2): six were missenses, three were located in splice-site regions, and two were frameshifts (Table 1).…”

“…The fifth missense, p.Leu139Arg, was identified in two Mexican children with NS, one SRNS, and one SSNS [41]. As in silico predictions were not performed for those variants in their original publications, we investigated their pathogenicity by predictive tools available, such as SIFT and PolyPhen-2.…”

“…Searches for NPHS2 mutations had been performed mainly in three countries: Mexico, Chile, and Brazil (Figure 1). In Mexico, only the 3rd exon of NPHS2 was sequenced in eight SRNS and five SSNS children [41]. The heterozygous p.Leu139Arg variant was identified in two patients, one SRNS and one SSNS; therefore, it was considered as a variant of unknown significance.…”