Academic Journal
Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40
| العنوان: | Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40 |
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| المؤلفون: | Morgan, Angela T, Scerri, Thomas S, Vogel, Adam P, Reid, Christopher A, Quach, Mara, Jackson, Victoria E, McKenzie, Chaseley, Burrows, Emma L, Bennett, Mark F, Turner, Samantha J, Reilly, Sheena, Horton, Sarah E, Block, Susan, Kefalianos, Elaina, Frigerio-Domingues, Carlos |
| بيانات النشر: | Oxford University Press (OUP) |
| سنة النشر: | 2023 |
| المجموعة: | Griffith University: Griffith Research Online |
| مصطلحات موضوعية: | Proteomics and metabolomics, Biomedical and clinical sciences, Health sciences, Psychology, PPID gene, brain MRI, chaperone, cyclophilin-40, stuttering |
| الوصف: | Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members. ; Full Text |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0006-8950 |
| Relation: | Brain; Morgan, AT; Scerri, TS; Vogel, AP; Reid, CA; Quach, M; Jackson, VE; McKenzie, C; Burrows, EL; Bennett, MF; Turner, SJ; Reilly, S; Horton, SE; Block, S; Kefalianos, E; Frigerio-Domingues, C; Sainz, E; Rigbye, KA; Featherby, TJ; Richards, KL; Kueh, A; Herold, MJ; Corbett, MA; Gecz, J; Helbig, I; Thompson-Lake, DGY; Liégeois, FJ; Morell, RJ; Hung, A; Drayna, D; Scheffer, IE; Wright, DK; Bahlo, M; Hildebrand, MS, Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40., Brain, 2023, 146 (12), pp. 5086-5097; http://hdl.handle.net/10072/427505 |
| DOI: | 10.1093/brain/awad314 |
| الاتاحة: | http://hdl.handle.net/10072/427505 https://doi.org/10.1093/brain/awad314 |
| Rights: | This work is covered by copyright. You must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a specified licence, refer to the licence for details of permitted re-use. If you believe that this work infringes copyright please make a copyright takedown request using the form at https://www.griffith.edu.au/copyright-matters. ; open access |
| رقم الانضمام: | edsbas.7E01F487 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00068950 |
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| DOI: | 10.1093/brain/awad314 |