Session Information
Date: Monday, September 23, 2019
Session Title: Genetics
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To report a novel heterozygous missense mutation of TGM6 in a patient with cerebellar ataxia.
Background: Mutations in TGM6 have been recently implicated in the pathogenesis of spinocerebellar ataxia type 35 (SCA35), a rare autosomal dominant disease, marked by cerebellar degeneration. The associated phenotype includes slow progressive postural instability and incoordination of gait, cerebellar dysarthria, dysmetria, saccadic slowing and pyramidal signs. TGM6, a member of the transglutaminase superfamily specifically expressed in the central nervous system, is involved in proteins cross-linking. Even though it is established that mutations of TGM6 described so far reduce transglutaminase activity, the precise molecular pattern impaired is still unclear.
Method: We performed a neurological evaluation and genetic analysis of a patient with late-onset, progressive cerebellar ataxia and pyramidal tract signs.
Results: A novel TGM6 heterozygous mutation (R342W) was detected in a patient with late-onset, progressive cerebellar ataxia, pyramidal tract signs, cerebellar dysarthria and ocular dysmetria. A cerebellar atrophy was confirmed by brain imaging. The mutation, located at a highly conserved position, was rare (AF= 0.02%) and predicted as pathogenic by in silico tools.
Conclusion: In summary, we described the clinical phenotype of an Italian SCA35 patient, who was confirmed to have a novel heterozygous missense mutation of TGM6. Despite its rare frequency among general population, we suggest to consider SCA35 genetic testing in case of undiagnosed cerebellar ataxia.
To cite this abstract in AMA style:
A. Manini, T. Bocci, E. Monfrini, D. Ronchi, M. Vizziello, G. Franco, A. de Rosa, F. Sartucci, A. Di Fonzo. A novel TGM6 heterozygous mutation in a patient with cerebellar ataxia [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/a-novel-tgm6-heterozygous-mutation-in-a-patient-with-cerebellar-ataxia/. Accessed September 7, 2024.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-novel-tgm6-heterozygous-mutation-in-a-patient-with-cerebellar-ataxia/