Francisco Del Caño-Ochoa, Bobby G Ng, Malak Abedalthagafi, Mohammed Almannai, Ronald D Cohn, Gregory Costain, Orly Elpeleg, Henry Houlden, Ehsan Ghayoor Karimiani, Pengfei Liu, M Chiara Manzini, Reza Maroofian, Michael Muriello, Ali Al-Otaibi, Hema Patel, Edvardson Shimon, V Reid Sutton, Mehran Beiraghi Toosi, Lynne A Wolfe, Jill A Rosenfeld, Hudson H Freeze, Santiago Ramón-Maiques
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...
May 28, 2020: Genetics in Medicine: Official Journal of the American College of Medical Genetics