| Popis: |
Background and aims Steroid-resistant nephrotic syndrome (SRNS) is the heriditary chronic disease which is characterised by oedema, massive proteinuria, hypo – and disproteinemia, gipoalbuminemia, giperlipidemia and lipiduria. The outcome is chronic renal failure, invalidism of patients and life duration reduction. The purpose of this research is revealing of genes pathogenic variants what associated with developing of hereditary kidney diseases united by SRNS symptom complex on the basis of designed diagnostics algorithm. Methods The research included 45 patients aged from 0 up to 6 years with possible SRNS. Diagnostics included several stages: 1) Sanger sequencing of the NPHS2 gene coding and adherent intronic areas; 2) analysis of genes target areas by method of the New Generation Sequencing (NGS); 3) confirmation of the revealed pathogenic variants by Sanger sequencing. For all novel mutations the bioinformatical analysis of pathogenicity in silico by means of the computer program Alamut Visual was performed. Results After performing of first stage NPHS2 gene mutations were revealed in 9 patients (20%). After NGS pathogenic variants were found in 26 (57,8%) patients. In total 27 various pathogenic variants were revealed, 10 (37%) of them were revealed for the first time in the world: NPHS1 (c.1673G>T (p.Arg558Leu)), NPHS2 (c.897G>C (p.Lys299Asn); c.275G>C (p.Gly92Arg)), PLCE1 (c.5738G>A (p.Arg1913Gln)), TRPC6, ACTN4, WT1 (c.1392C>A (p.Asp464Glu)), COL4A3 (c.4021C>T (p.Pro1341Ser)), COL4A4 (c.2399C>G (p.Pro800Arg)), COL4A5, CD2AP, COQ2 (c.571–1G>A), COQ6 (c.1078C>T (p.Arg360Trp); c.1235A>G (p.Tyr412Cys)). Conclusions Revealing of novel mutations in various genes allows us to say about appreciable genetic heterogeneity of SRNS in the Russian Federation. The developed diagnostic panel has high resolving power as in total mutations were found in 77,8% of studied patients. |
