Expanding the phenotype of TARDBP mutation in a Tunisian family with clinical phenotype heterogeneity

Abstract

We describe a Tunisian family carrier of the same rare mutation in TARDBP but developing different neurodegenerative disease with heterogenous features. We explored the possible genetic modifiers leading to the observed intrafamilial phenotypic variability. Genetic analysis identified TARDBP p.G294A mutation among4 members. Additionally, the ALS case was muted in GBA. While the three cases of AD were carriers of PRKN and GBA mutations. Finally, the FTD-parkinsonism patient was mutated for LRRK2 p.G2019S that might increase his susceptibility to develop Parkinsonism spectrum. Genetic variants of TARDBP may influence the clinical manifestation in ALS case.

Keywords:

• TARDBP
• oligogenic profile
• inbreeding
• heterogeneity
• modulators
• biomarker
• DNA
• genetics

Acknowledgments

The authors thank the patients who gave their consent and participated in the present study and were extremely collaborative. The authors are grateful to the technical assistance given in the platform of sequencing in faculty of medicine of Tunis.

Ethical approval

All subjects conformed to the principles outlined in the Declaration of Helsinki and the study have been performed with permission of the Razi hospital ethic committee. All patients were informed about the purposes of the study and gave their written consent to participate.

Declaration of interest

No potential conflict of interest was reported by the author(s).