{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wong HH"],"funding":["National Institute of Neurological Disorders and Stroke","International Rett Syndrome Foundation","Howard Hughes Medical Institute","Government of Singapore Ministry of Education","Uehara Memorial Foundation","National Medical Research Council","The Rockefeller University","Procter & Gamble","National Human Genome Research Institute","St Giles Foundation","National Research Foundation of Singapore","Muscular Dystrophy Association","INSERM","NHGRI NIH HHS","NINDS NIH HHS","A*STAR","NIGMS NIH HHS"],"pagination":["1301-1317"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8322802"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["108(7)"],"pubmed_abstract":["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 m"],"journal":["American journal of human genetics"],"pubmed_title":["Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy."],"pmcid":["PMC8322802"],"funding_grant_id":["UM1 HG006542","R35 NS105078","P41 GM108538","R35 GM131795","U54 HG006542"],"pubmed_authors":["Teoh TS","Zhang S","Sirota FL","Eyaid W","Unal S","Liang C","Maroofian R","Bauer P","Xue S","Gilani N","Ali NA","Yılmaz E","Kayserili H","Seyedpour S","Lupski JR","Paul F","Houlden H","Choo SC","Arman-Bilir O","Isıkay S","Rezaei N","Ceylaner S","Wong HH","Casanova JL","Loh AYT","Mbarek H","Pehlivan D","Pagliarini DJ","Ho L","Traspas RM","Ly TTN","Maurer-Stroh S","Chia CY","Sng D","Cepni E","Bertoli-Avella A","Mathuru AS","Shishkova E","Bard FA","Gleeson JG","Gumruk F","Boisson B","Khotaei GT","Reversade B","Tripolszki K","Chaabouni M","Zaki MS","Lee C","Hasbini D","Cetinkaya A","Laine C","Yarali N","Ugurlu Ci Men D","Gurel A","Akarsu NA","Sotiropoulou K","Georgiadou D","Simsek-Kiper PO","Keng SS","Efthymiou S","Rensvold J","Chai G","Coon JJ","Isfort RJ","Talim B","Maier M","Bascom CC","Nathan FM","Seet SH","Ordonez N","Mitani T","Alsubhi A"],"additional_accession":[]},"is_claimable":false,"name":"Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.","description":"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 m","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Jul","modification":"2026-05-08T00:53:53.146Z","creation":"2022-02-11T14:21:55.496Z"},"accession":"S-EPMC8322802","cross_references":{"pubmed":["34038740"],"doi":["10.1016/j.ajhg.2021.05.003"]}}