BOLALARDA STEROIDGA REZISTENT NEFROTIK SINDROMNING GENETIK ASOSLARI VA UNING KLINIK KORRELYATSIYALARI
##article.subject##:
steroidga rezistent nefrotik sindrom; NGS; COL4A; Alport sindromi; pediatrik nefrologiya.##article.abstract##
Kirish. Steroidga rezistent nefrotik sindrom (SRNS) buyrak kasalligining terminal bosqichigacha (terminal bosqichdagi surunkali buyrak kasalligi) progressiyalanish xavfi yuqori bo‘lgan holat hisoblanadi. Yangi avlod sekvenslash texnologiyalari (Next-Generation Sequencing, NGS) yordamida bolalardagi ko‘plab holatlar monogen tabiatga ega ekanligi aniqlangan bo‘lib, bu davolash taktikasi va kasallik prognoziga bevosita ta’sir ko‘rsatadi.
Tadqiqot maqsadi. Bolalar milliy tibbiyot markazi kogortasida pediatrik SRNS va tug‘ma nefrotik sindrom (TNS) bilan og‘rigan bemorlarda mutatsiyalar spektrini tavsiflash hamda genotip–fenotip assotsiatsiyalarini o‘rganish.
Materiallar va usullar. Tasdiqlangan SRNS yoki CNS tashxisi qo‘yilgan 54 nafar pediatrik bemorda NGS ning maqsadli gen paneli yordamida genetik tekshiruv o‘tkazildi. Assotsiatsiyalarni baholash uchun Mann–Whitney U testi, χ² testi va Fisherning aniq testi qo‘llanildi.
Natijalar. Tadqiqotga genetik jihatdan tasdiqlangan SRNS yoki CNS bilan og‘rigan 54 nafar bola kiritildi. Jami 34 ta turli genetik variant aniqlandi. COL4A oilasiga mansub genlar mutatsiyalari (COL4A3/4/5) eng ko‘p uchragan guruh bo‘ldi (27,8%). COL4A5 eng ko‘p aniqlangan alohida gen bo‘lib (14,8%), u o‘g‘il bolalarda sezilarli ustunlik bilan kuzatildi (M:F = 7:1; OR = 4,32; p = 0,038). CNS bilan og‘rigan bemorlar SRNS bemorlariga nisbatan statistik jihatdan sezilarli darajada yoshroq edi (p = 0,022). COQ2 genidagi mutatsiyalar 5,6% holatni tashkil etdi va ularning barchasi CNS shaklida namoyon bo‘ldi. Digеn mutatsiyalar bemorlarning 20,4% ida aniqlangan.
Xulosa. Pediatrik SRNS genetik tuzilmasida COL4A mutatsiyalari ustunlik qiladi, bu esa g‘arbiy kohortalardan farq qiladi, chunki ularda NPHS2 mutatsiyalari ko‘proq uchraydi. SRNS bilan og‘rigan barcha pediatrik bemorlarda keng qamrovli genetik panel tekshiruvi standart diagnostik yondashuv sifatida qo‘llanishi lozim.
Библиографические ссылки
Trautmann A, Vivarelli M, Samuel S, et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2020;35(6):1529–1561.
Bierzynska A, Soderquest K, Koziell A. Genes and podocytes - new insights into mechanisms of podocytopathy. Front Endocrinol. 2017;7:186.
Vivante A, Hildebrandt F. Exploring the genetic basis of early-onset chronic kidney disease. Nat Rev Nephrol. 2016;12(3):133–146.
Lovric S, Ashraf S, Tan W, Hildebrandt F. Genetic testing in steroid-resistant nephrotic syndrome: when and how? Nephrol Dial Transplant. 2016;31(11):1802–1813.
Nagano C, Yamamura T, Horinouchi T, et al. Comprehensive genetic diagnosis of Japanese patients with severe proteinuria. Sci Rep. 2020;10(1):11285.
Daga S, Donati F, Capitani K, et al. New frontiers to cure Alport syndrome: COL4A3 and COL4A4 mutations sorted by predicted protein structural-functional alterations. J Nephrol. 2021;34(4):1104–1115.
Gast C, Pengelly RJ, Lyon M, et al. Collagen (COL4A) mutations are the most frequent mutations underlying adult focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2016;31(6):961–970.
Wang F, Zhang Y, Mao J, et al. Spectrum of mutations in Chinese children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2017;32(7):1207–1221.
Sadowski CE, Lovric S, Ashraf S, et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2015;26(6):1279–1289.
Büscher AK, Habbig S, Kranz B, et al. Loss-of-function mutations in ITSN2 cause autosomal recessive nephrotic syndrome. Kidney Int. 2022;101(3):569–580.
