{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Del Cano-Ochoa F"],"funding":["NIDDK NIH HHS","NINDS NIH HHS","MICIU"],"pagination":["1598-1605"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7521996"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(10)"],"pubmed_abstract":["Purpose
Pathogenic autosomal recessive variants in CAD, encoding the multienzymatic protein initiating pyrimidine de novo biosynthesis, cause a severe inborn metabolic disorder treatable with a dietary supplement of uridine. This condition is difficult to diagnose given the large size of CAD with over 1000 missense variants and the nonspecific clinical presentation. We aimed to develop a reliable and discerning assay to assess the pathogenicity of CAD variants and to select affected individuals that might benefit from uridine therapy.Methods
Using CRISPR/Cas9, we generated a human CAD-knockout cell line that requires uridine supplements for survival. Transient transfection of the knockout cells with recombinant CAD restores growth in absence of uridine. This system determin"],"journal":["Genetics in medicine : official journal of the American College of Medical Genetics"],"pubmed_title":["Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy."],"pmcid":["PMC7521996"],"funding_grant_id":["R01DK99551","BFU2016-80570-R","U54 NS115198","R01 DK099551","R01 NS109149"],"pubmed_authors":["Houlden H","Elpeleg O","Karimiani EG","Almannai M","Rosenfeld JA","Muriello M","Liu P","Toosi MB","Maroofian R","Costain G","Del Cano-Ochoa F","Wolfe LA","Ramon-Maiques S","Abedalthagafi M","Ng BG","Sutton VR","Cohn RD","Al-Otaibi A","Shimon E","Patel H","Freeze HH","Manzini MC"],"additional_accession":[]},"is_claimable":false,"name":"Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy.","description":"Purpose
Pathogenic autosomal recessive variants in CAD, encoding the multienzymatic protein initiating pyrimidine de novo biosynthesis, cause a severe inborn metabolic disorder treatable with a dietary supplement of uridine. This condition is difficult to diagnose given the large size of CAD with over 1000 missense variants and the nonspecific clinical presentation. We aimed to develop a reliable and discerning assay to assess the pathogenicity of CAD variants and to select affected individuals that might benefit from uridine therapy.Methods
Using CRISPR/Cas9, we generated a human CAD-knockout cell line that requires uridine supplements for survival. Transient transfection of the knockout cells with recombinant CAD restores growth in absence of uridine. This system determin","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2026-05-01T01:01:28.91Z","creation":"2020-10-29T09:32:50Z"},"accession":"S-EPMC7521996","cross_references":{"pubmed":["32461667"],"doi":["10.1038/s41436-020-0833-2"]}}