Background: Mutations in TGM6 gene, encoding for transglutaminase 6 (TG6), have been implicated in the pathogenesis of spinocerebellar ataxia type 35 (SCA35), a rare autosomal dominant disease marked by cerebellar degeneration and characterized by postural instability, incoordination of gait, features of cerebellar dysfunction and pyramidal signs. Case presentation: Here we report the case of an Italian patient with late-onset, slowly progressive cerebellar features, including gait ataxia, scanning speech and ocular dysmetria and pyramidal tract signs. Whole exome sequencing revealed the rare heterozygous c.1024C > T (p.R342W) variant of TGM6, located at a highly evolutionary conserved position and predicted as pathogenic by in silico tools. Expression of TG6-R342W mutant in HEK293T cells led to a significant reduction of transamidase activity compared to wild-type TG6. Conclusion: This finding extends SCA35 genetic landscape, highlighting the importance of TGM6 screening in undiagnosed late-onset and slowly progressive cerebellar ataxias.
A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation / A. Manini, T. Bocci, A. Migazzi, E. Monfrini, D. Ronchi, G. Franco, A. De Rosa, F. Sartucci, A. Priori, S. Corti, G.P. Comi, N. Bresolin, M. Basso, A. Di Fonzo. - In: BMC NEUROLOGY. - ISSN 1471-2377. - 20:1(2020 Nov 07).
|Titolo:||A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation|
MANINI, ARIANNA (Primo)
BOCCI, TOMMASO (Secondo)
BASSO, MANUELA (Penultimo)
|Parole Chiave:||Case report; SCA35; Spinocerebellar ataxias; TGM6; Transglutaminase|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||7-nov-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1186/s12883-020-01964-1|
|Appare nelle tipologie:||01 - Articolo su periodico|