29 research outputs found
Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy
Summary
Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems
Granulomatosis with polyangiitis and pregnancy: Anti‐neutrophil cytoplasmic antibody, placental inflammation, chorangiosis and pre‐eclampsia
THE PREDICTOR FOR DISEASE SPECIFIC-QUALITY OF LIFE IN PATIENTS WITH HIP AND KNEE OSTEOARTHRITIS: MENTAL HEALTH
WOS: 00021579910124
Mesenchymal stem cell studies in children with inherited diseases: A proposal for identification of candidate diseases for mesenchymal stem cell therapies (PEDI-STEM project)
The Prevalence Of Homozygous Mthfr Polymorphism(S) In A Turkish University Hospital Population That Necessitated Mthfr Polymorphism Investigation
Scopu
Sorafenib-induced Posterior Reversible Encephalopathy Syndrome in a Child With FLT3-ITD-positive Acute Myeloid Leukemia
Wo