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 / Manini, A.; Bocci, T.; Migazzi, A.; Monfrini, E.; Ronchi, D.; Franco, G.; De Rosa, A.; Sartucci, F.; Priori, A.; Corti, S.; Comi, G. P.; Bresolin, N.; Basso, M.; Di Fonzo, A.. - In: BMC NEUROLOGY. - ISSN 1471-2377. - 20:1(2020), p. 408. [10.1186/s12883-020-01964-1]
A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation
Migazzi A.;Basso M.;
2020-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione
