Frederike L Harms, Alexander J M Dingemans, Maja Hempel, Rolph Pfundt, Tatjana Bierhals, Christian Casar, Christian Müller, Jikke-Mien F Niermeijer, Jan Fischer, Arne Jahn, Christoph Hübner, Silvia Majore, Emanuele Agolini, Antonio Novelli, Jasper van der Smagt, Robert Ernst, Ellen van Binsbergen, Grazia M S Mancini, Marjon van Slegtenhorst, Tahsin Stefan Barakat, Emma L Wakeling, Arveen Kamath, Lilian Downie, Lynn Pais, Susan M White, Bert B A de Vries, Kerstin Kutsche
PURPOSE: The SF3B splicing complex is composed of SF3B1-6 and PHF5A. We report a developmental disorder caused by de novo variants in PHF5A. METHODS: Clinical, genomic, and functional studies using subject-derived fibroblasts and a heterologous cellular system were performed. RESULTS: We studied nine subjects with congenital malformations, including preauricular tags and hypospadias, growth abnormalities, and developmental delay who had de novo heterozygous PHF5A variants, including four loss-of-function (LOF), three missense, one splice, and one start-loss variant...
July 6, 2023: Genetics in Medicine: Official Journal of the American College of Medical Genetics