Journal article
Pathogenic variants in nucleoporin TPR (translocated promoter region, nuclear basket protein) cause severe intellectual disability in humans
NJ Van Bergen, KM Bell, K Carey, R Gear, S Massey, EK Murrell, L Gallacher, K Pope, PJ Lockhart, A Kornberg, L Pais, M Walkiewicz, C Simons, VO Wickramasinghe, SM White, J Christodoulou
Human Molecular Genetics | Published : 2022
DOI: 10.1093/hmg/ddab248
Abstract
The nuclear pore complex (NPC) is a multi-protein complex that regulates the trafficking of macromolecules between the nucleus and cytoplasm. Genetic variants in components of the NPC have been shown to cause a range of neurological disorders, including intellectual disability and microcephaly. Translocated promoter region, nuclear basket protein (TPR) is a critical scaffolding element of the nuclear facing interior of the NPC. Here, we present two siblings with biallelic variants in TPR who present with a phenotype of microcephaly, ataxia and severe intellectual disability. The variants result in a premature truncation variant, and a splice variant leading to a 12-amino acid deletion respec..
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Awarded by National Human Genome Research Institute
Funding Acknowledgements
The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to J.C. is generously supported by the Royal Children's Hospital Foundation. UDP-Vic acknowledges financial support from the Murdoch Children's Research Institute and the Harbig Foundation. The Rare Disease Flagship acknowledges financial support from the Royal Children's Hospital Foundation, the Murdoch Children's Research Institute and the Harbig Foundation. Sequencing and analysiswere provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. VOW is supported by a Veski Innovation Fellowship and a mid-career fellowship from the Victorian Cancer Agency and funding from NHMRC (GNT1127745, 2003542 and 2003545).