A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation

Arianna Manini, Tommaso Bocci, Alice Migazzi, Edoardo Monfrini, Dario Ronchi, Giulia Franco, Anna De Rosa, Ferdinando Sartucci, Alberto Priori, Stefania Corti, Giacomo Pietro Comi, Nereo Bresolin, Manuela Basso, Alessio Di Fonzo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number408
JournalBMC Neurology
Volume20
Issue number1
DOIs
Publication statusPublished - Dec 1 2020

Keywords

  • Case report
  • SCA35
  • Spinocerebellar ataxias
  • TGM6
  • Transglutaminase

ASJC Scopus subject areas

  • Clinical Neurology

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