Quels sont les effets des tests génétiques sur les patients? Angoisse, culpabilité, déni, les situations sont diverses, en fonction des personnes et des pathologies. Il est donc indispensable que les généticiens et les psychologues travaillent ensemble pour assurer le suivi de ceux qui deviennent brusquement des patients potentiels.
The low uptake of presymptomatic testing in Huntington disease prompted us to question family members on how they handle the transmission of information regarding genetic risk. We hypothesised that in 2019, parents would inform their at-risk children about their genetic risk more and at a younger age than in 2000, given the availability of prenatal diagnosis, French legislation changes since 2011, and recent therapeutic advances. We made a questionnaire available about the transmission of genetic information within families with Huntington disease in 2000 and 2019. We obtained 443 questionnaires (295 in 2019 and 148 in 2000). Participants were mainly at-risk for Huntington disease (n = 113), affected (n = 85), and spouses (n = 154). In 2019, participants had a higher mean education level (p < 0.01) and a mean age of 44.1 ± 15.1 years (vs 48.1 ± 11.4 years in 2000, p < 0.01). They had been informed about the risk of being a carrier at around 30 years of age (29.0 ± 14.2 in 2019 vs 32.2 ± 13.8 in 2000, p = 0.09). However, they would inform at an earlier age (≤18 years, 67% vs 59%, p = 0.16). Information on transmission risk had been given primarily by parents (45% vs 30%, p = 0.06). In addition, genetic testing for relatives unaware of their status was recommended more frequently in 2019 (46% vs 32%, p < 0.001). Respondents in 2019 recommended genetic testing more often but overall attitudes towards information and testing have not changed significantly over the 19-year time period since the questionnaire was first delivered even despite recent clinical trials potential disease modifying therapies.
With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity-to-onset and, potentially, treatment-response markers in both human and preclinical SCA3 trials. ; Acknowledgements: This work was supported by the Horizon 2020 research and innovation programme (grant 779257 Solve-RD to MS and RS), the National Ataxia Foundation (grant to CW and MS), the Wilhelm Vaillant Stiftung (grant to CW), the EU Joint Programme—Neurodegenerative Disease Research (JPND) through participating national funding agencies, and the European Union's Horizon 2020 research and innovation programme under grant agreement No 643417. BM was supported in part from the grant NKFIH 119540. HJ was funded by the Medical Faculty of the University of Heidelberg. CB was funded by the University of Basel (PhD Program in Health Sciences). The funding sources had no role in the study design, data collection, data analysis, data interpretation or writing of the manuscript.