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. 2025 Apr;32(4):e70104.
doi: 10.1111/ene.70104.

TTR Gene Screening Since the Advent of Biotherapies in France: A Nationwide Retrospective Survey Between 2018 and 2023

Abd El Kader Ait Tayeb  1   2   3 , Pauline Chazelas  4   5 , Vianney Poinsignon  1 , David Adams  6   7   8 , Caroline Berthot  1   2 , Cécile Cauquil  6 , Claire-Marie Dhaenens  9 , Bruno Francou  1   10 , Guillaume Jedraszak  11   12 , Céline Labeyrie  6   7   8 , Clara Laffitte Redondo  1 , Anne-Sophie Lia  4   5 , Maureen Lopez  1 , Alexis Proust  1 , Franck Sturtz  4   5 , Lucie Tosca  1   2 , Céline Verstuyft  1   13 , Andoni Echaniz-Laguna  6   7   8 , Jérôme Bouligand  1   2
Affiliations

TTR Gene Screening Since the Advent of Biotherapies in France: A Nationwide Retrospective Survey Between 2018 and 2023

Abd El Kader Ait Tayeb et al. Eur J Neurol. 2025 Apr.

Abstract

Background: Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disorder caused by mutations in the TTR gene. Associated with various clinical phenotypes like polyneuropathy and cardiomyopathy, ATTRv has historically had poor outcomes. Recent advances in biotherapies have significantly improved these outcomes. This study aimed to assess the evolution in genetic TTR variant screening since the advent of biotherapies in France in 2018.

Methods: This nationwide retrospective study analyzed data and genetic results from patients who underwent TTR gene sequencing from 2018 to 2023.

Results: 16,640 patients were tested during the period studied. There was a 108% increase in the number of TTR gene sequencing performed annually between 2018 and 2023. Positive rates remained stable despite increased testing (7.09% over time). During this 6-year period, 1,179 patients were diagnosed with a pathogenic variant of TTR.

Conclusions: The study shows a substantial rise in TTR genetic testing in France, likely linked to the deployment of biotherapies. These findings underscore the necessity of integrating TTR gene sequencing into standard diagnostic procedures, especially given the effectiveness of treatments and the stability of positive rates.

Keywords: TTR gene; amyloidosis; epidemiology; nationwide survey; transthyretin.

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Conflict of interest statement

Prof. Echaniz‐Laguna received consulting fees from Alnylam Pharmaceuticals, Akcea Therapeutics, AstraZeneca, and Pfizer. Docteur Labeyrie received consulting fees and a speech honorarium from Alnylam Pharmaceuticals and Pfizer. Dr. Cauquil received consulting fees and a speech honorarium from Pfizer, Alnylam Pharmaceuticals, and AstraZeneca. Pr. Adams received consulting fees from Pfizer, Alnylam, Astrazeneca, BridgeBio, and payment of transport costs for the ISA congress from Alnylam. A.E.K.A.T., P.C., V.P., C.B., C.‐M.D., B.F., C.L.R., G.J., A.‐S.L., M.L., A.P., F.S., L.T., C.V., and J.B. declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Evolution of the number of patients tested for a genetic TTR variant each year between 2018 and 2023. Variations in the number of tests performed were provided as percentages and calculated in relation to the reference year (2018).
FIGURE 2
FIGURE 2
Evolution of the number of patients carrying a genetic “likely pathogenic” or “pathogenic” TTR variant each year between 2018 and 2023. Variations in the number of tests performed were provided as percentages and calculated in relation to the reference year (2018).
FIGURE 3
FIGURE 3
Evolution of the rate of positive tests for genetic testing of TTR between 2018 and 2023. A positive test was defined as a sequencing revealing a “likely pathogenic” or “pathogenic” variant of TTR according to ACMG criteria—χ 2 test was performed.
See this image and copyright information in PMC

References

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Supplementary concepts