Karla P Figueroa, Caspar Gross, Elena Buena-Atienza, Sharan Paul, Mandi Gandelman, Naseebullah Kakar, Marc Sturm, Nicolas Casadei, Jakob Admard, Joohyun Park, Christine Zühlke, Yorck Hellenbroich, Jelena Pozojevic, Saranya Balachandran, Kristian Händler, Simone Zittel, Dagmar Timmann, Friedrich Erdlenbruch, Laura Herrmann, Thomas Feindt, Martin Zenker, Thomas Klopstock, Claudia Dufke, Daniel R Scoles, Arnulf Koeppen, Malte Spielmann, Olaf Riess, Stephan Ossowski, Tobias B Haack, Stefan M Pulst
Despite linkage to chromosome 16q in 1996, the mutation causing spinocerebellar ataxia type 4 (SCA4), a late-onset sensory and cerebellar ataxia, remained unknown. Here, using long-read single-strand whole-genome sequencing (LR-GS), we identified a heterozygous GGC-repeat expansion in a large Utah pedigree encoding polyglycine (polyG) in zinc finger homeobox protein 3 (ZFHX3), also known as AT-binding transcription factor 1 (ATBF1). We queried 6,495 genome sequencing datasets and identified the repeat expansion in seven additional pedigrees...
April 29, 2024: Nature Genetics