Prikazujemo obiteljski oblik balansirane translokacije t(7;14) koji je nađen u majke i dva njezina sina. Majka je imala samo šum nad aortnim ušćem bez hemodinamskog značenja, djeca su imala gotovo ...istovjetan klinički nalaz; značajnu supravalvularnu aortnu stenozu tipa pješćanog sata, intrakavitarnu stenozu u lijevoj klijetki i multiple periferne pulmonalne stenoze. Nisu imali niti jedan drugi klinički znak Williams-Beurenova sindroma, osim vjerojatno dubokog metaličnog glasa.
Konvencionalna kromosomska analiza neočekivano je pokazala da je riječ o balansiranoj translokaciji t(7;14), identična translokacija pronađena je u majke i brata. Fluorescentna in situ hibridizacija s WSCR probama pokazala je da je prijelomna točka uzdužno pocijepala elastinsku regiju u sve troje ispitanika. Kariotip ispitanika interpretiran je prema ISCN-u kao
46,XY,t(7;14)(q11.23;p12).ish t(7;14)(D7Z1+,ELNsp;D14Z1/D22Z1+,ELNsp+)mat. Drugim riječima, translokacija je pocijepala elastinsku regiju, što može biti razlogom nastanka razvojnih anomalija karakterističnih za Williams-Beurenov sindrom.
Pregledom kroz literaturu našli smo da ovakav nalaz nije dosad objavljen u genetičkoj obradi supravalvularne aortne stenoze, odnosno Williams-Beurenova sindroma ili stanja koja se ne mogu razvrstati u ove dvije krajnje kategorije zbog šarolikosti fenotipskih karakteristika.
Secondary infections contribute significantly to covid-19 mortality but driving factors remain poorly understood. Autopsies of 20 covid-19 cases and 14 controls from the first pandemic wave ...complemented with microbial cultivation and RNA-seq from lung tissues enabled description of major organ pathologies and specification of secondary infections. Lethal covid-19 segregated into two main death causes with either dominant diffuse alveolar damage (DAD) or secondary pneumonias. The lung microbiome in covid-19 showed a reduced biodiversity and increased prototypical bacterial and fungal pathogens in cases of secondary pneumonias. RNA-seq distinctly mirrored death causes and stratified DAD cases into subgroups with differing cellular compositions identifying myeloid cells, macrophages and complement C1q as strong separating factors suggesting a pathophysiological link. Together with a prominent induction of inhibitory immune-checkpoints our study highlights profound alterations of the lung immunity in covid-19 wherein a reduced antimicrobial defense likely drives development of secondary infections on top of SARS-CoV-2 infection.
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•Covid-19 autopsy cohort complemented with microbial cultivation and deep sequencing•Major death causes stratify into DAD and secondary pneumonias•Prototypical bacterial and fungal agents are found in secondary pneumonias•Macrophages and C1q stratify DAD subgroups and indicate immune impairment in lungs
Immunology; Virology; Microbiome
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