Investigating the pathogenicity of the transglutaminase 6 L517W variant


  • Nonsegregation of the transglutaminase 6 gene (TGM6) p.L517W mutation with disease phenotype suggests that the variant is not pathogenic.

  • In the four-generation pedigree studied, ataxia was likely caused by a CAG expansion in atrophin-1 (ATN1).

Why this matters

  • Pathogenic mutations in TGM6 have previously been reported in people with spinocerebellar ataxia 35 (SCA35).

  • Findings from this study challenge the role of TGM6 in SCA35 pathogenesis.