Clara D M van Karnebeek, Maja Tarailo-Graovac, René Leen, Rutger Meinsma, Solenne Correard, Judith Jansen-Meijer, Sergey V Prykhozhij, Izabella A Pena, Kevin Ban, Sarah Schock, Vishal Saxena, Mia L Pras-Raves, Britt I Drögemöller, Anita E Grootemaat, Nicole N van der Wel, Doreen Dobritzsch, Winfried Roseboom, Bauke V Schomakers, Yorrick R J Jaspers, Lida Zoetekouw, Jeroen Roelofsen, Carlos R Ferreira, Robin van der Lee, Colin J Ross, Jakub Kochan, Rebecca L McIntyre, Jan B van Klinken, Michel van Weeghel, Gertjan Kramer, Bernhard Weschke, Philippe Labrune, Michèl A Willemsen, Daria Riva, Barbara Garavaglia, John B Moeschler, James J Filiano, Marc Ekker, Jason N Berman, David Dyment, Frédéric M Vaz, Wyeth W Wassermann, Riekelt H Houtkooper, André B P van Kuilenburg
The functionality of many cellular proteins depends on cofactors, yet they have only been implicated in a minority of Mendelian diseases. Here, we describe the first two inherited disorders of the cytosolic iron-sulfur protein assembly system METHODS: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences RESULTS: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD...
February 24, 2024: Genetics in Medicine: Official Journal of the American College of Medical Genetics