INTRODUCTION AND METHODS: We report two series of individuals with DDX3X variations, one (48 individuals) from physicians and one (44 individuals) from caregivers. RESULTS: These two series include several symptoms in common, with fairly similar distribution, which suggests that caregivers' data are close to physicians' data. For example, both series identified early childhood symptoms that were not previously described: feeding difficulties, mean walking age, and age at first words. DISCUSSION: Each of the two datasets provides complementary knowledge. We confirmed that symptoms are similar to those in the literature and provides more details on feeding difficulties. Caregivers considered that the symptom attention-deficit/hyperactivity disorder were most worrisome. Both series also reported sleep disturbance. Recently, anxiety has been reported in individuals with DDX3X variants. We strongly suggest that attention-deficit/hyperactivity disorder, anxiety, and sleep disorders need to be treated.

• Klíčová slova
• DDX3X, ADHD, caregivers, developmental milestones,
• MeSH
• DEAD-box RNA-helikasy MeSH
• hyperkinetická porucha * genetika   terapie   MeSH
• kojenec MeSH
• lidé MeSH
• osoby pečující o pacienty * MeSH
• předškolní dítě MeSH
• zpráva o sobě MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DDX3X protein, human MeSH Prohlížeč
• DEAD-box RNA-helikasy MeSH

DDX3X is a ubiquitously expressed RNA helicase involved in multiple stages of RNA biogenesis. DDX3X is frequently mutated in Burkitt lymphoma, but the functional basis for this is unknown. Here, we show that loss-of-function DDX3X mutations are also enriched in MYC-translocated diffuse large B cell lymphoma and reveal functional cooperation between mutant DDX3X and MYC. DDX3X promotes the translation of mRNA encoding components of the core translational machinery, thereby driving global protein synthesis. Loss-of-function DDX3X mutations moderate MYC-driven global protein synthesis, thereby buffering MYC-induced proteotoxic stress during early lymphomagenesis. Established lymphoma cells restore full protein synthetic capacity by aberrant expression of DDX3Y, a Y chromosome homolog, the expression of which is normally restricted to the testis. These findings show that DDX3X loss of function can buffer MYC-driven proteotoxic stress and highlight the capacity of male B cell lymphomas to then compensate for this loss by ectopic DDX3Y expression.

• Klíčová slova
• Burkitt lymphoma, DDX3X, MYC, RNA helicase, germinal center, proteotoxic stress, translation,
• MeSH
• B-buněčný lymfom enzymologie   genetika   patologie   MeSH
• B-lymfocyty enzymologie   patologie   MeSH
• DEAD-box RNA-helikasy genetika   metabolismus   MeSH
• dítě MeSH
• dospělí MeSH
• homeostáze proteinů MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace ztráty funkce MeSH
• myši transgenní MeSH
• nádorové buněčné linie MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• předškolní dítě MeSH
• proteom MeSH
• proteosyntéza MeSH
• protoonkogenní proteiny c-myc genetika   metabolismus   MeSH
• regulace genové exprese enzymů MeSH
• regulace genové exprese u nádorů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stres endoplazmatického retikula MeSH
• vedlejší histokompatibilní antigeny genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DDX3X protein, human MeSH Prohlížeč
• DDX3Y protein, human MeSH Prohlížeč
• DEAD-box RNA-helikasy MeSH
• MYC protein, human MeSH Prohlížeč
• nádorové proteiny MeSH
• proteom MeSH
• protoonkogenní proteiny c-myc MeSH
• vedlejší histokompatibilní antigeny MeSH