20.500.12556/DKUM-97534 Pridobljena mutacija p.d816v v genu kit in genotipizacija triptaznega lokusa pri otrocih s kožno mastocitozo KIT p.D816V mutation in peripheral blood and tryptase locus genotyping in pediatric patients with cutaneous mastocytosis Dedna α-triptazemija je genetska lastnost, ki nastane zaradi povečanega števila kopij gena, ki kodira α-triptazo, in je povezana z mastocitozo pri odraslih. Namen raziskave je bil oceniti povezavo med α-triptazo in mastocitozo v pediatrični populaciji ter preveriti, ali mutacija KIT p.D816V v levkocitih periferne krvi napoveduje sistemsko bolezen pri otrocih. V prospektivno kohorto je bilo vključenih 68 otrok s kožno mastocitozo, obravnavanih v terciarnem centru v Sloveniji. Genotipizacija triptaze je bila opravljena z metodo kapljičnega digitalnega PCR, prisotnost mutacije KIT p.D816V v levkocitih periferne krvi pa smo določali z visoko občutljivim PCR-testom. Večina bolnikov (57 od 68; [83,8 %]) je imela vsaj eno kopijo gena za α-triptazo; pri nobenem nismo potrdili dedne α-triptazemije. Med bolniki s pozitivnim izvidom za KIT p.D816V v levkocitih periferne krvi (7/68; [10,3%] je eden izpolnjeval diagnostična merila za indolentno sistemsko mastocitozo, pri drugem pa smo postavili diagnozo monoklonskega sindroma aktivacije mastocitov. Eden izmed teh je imel tudi povišano koncentracijo bazalne serumske triptaze (14,5 ng/mL). Ugotovili smo visoko prisotnost zarodne α-triptaze pri otrocih z mastocitozo, ne pa dedne α-triptazemije. Rezultati, z uporabo občutljivega določanja mutacije KIT p.D816V kažejo, da je lahko prisotnost mutacije KIT p.D816V v periferni krvi pokazatelj sistemske bolezni pri otrocih s kožno mastocitozo. Hereditary α-tryptasemia a genetic trait caused by increased α-tryptase-encoding typtase alpha/beta-1 copy number-is associated with adult mastocytosis. The primary objective was to assess the association between α-tryptase and pediatric mastocytosis. We also want to evaluate whether the KIT p.D816V mutation in peripheral blood leukocytes reliably predicts systemic mastocytosis in children. A prospective cohort of 68 children from a referral center in Slovenia with cutaneous mastocytosis underwent tryptase genotyping by droplet digital PCR and examination for KIT p.D816V in PBL using a sensitive PCR test. A significant majority of patients (57 of 68; [83.8%]) had at least one α-tryptase-encoding gene; none had HαT. 7 of the 68 (10.3%) who were positive for KIT p.D816V in PBL, one fulfilled diagnostic criteria for indolent systemic mastocytosis, and another was diagnosed with monoclonal mast cell activation syndrome. One of those individuals had an increased basal serum tryptase level (14.5 ng/mL). We found a high presence of germline α-tryptase in children with cutaneous mastocytosis, but not hereditary α-tryptasemia. By employing sensitive examination for KIT p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that KIT p.D816V in peripheral blood leukocytes may indicate systemic disease in children with cutaneous mastocytosis . KIT D816V dedna α-triptazemija mastocitoza pediatrija periferna kri kostni mozeg KIT D816V hereditary α-tryptasemia mastocytosis pediatrics peripheral blood bone marrow true true false [O. Točkova] Slovenski jezik Angleški jezik Doktorska disertacija 2026-03-16 15:57:58 2026-08-06 14:21:45 2026-08-07 03:07:34 0000-00-00 00:00:00 2026 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.5-053.2-056-097:577.27(043.3) 285941507 DOK_Tockova_Olga_2026.pdf DOK_Tockova_Olga_2026.pdf 1 A54832D94752976CAA791F7011791F85 5acb7bdb669cafc45edfac82609d18fd33912aa3a9f4e04f201d086edff1f0cb 3ea65633-85bb-11f1-a66a-00155d580e34 https://dk.um.si/Dokument.php?lang=slv&id=208504 Medicinska fakulteta 0 0 0