Refine penetrance estimates in the main pathogenic variants of transthyretin hereditary (familial) amyloid polyneuropathy (TTR-FAP) using a new non-parametric approach (NPSE)

Farida Gorram (1, 2) , Flora Alarcon (3) , Hervé Perdry (4) , Bérénice Hébrard (2) , Thibaud Damy (1) , Pascale Fanen (5) , Benoît Funalot (6) , Gregory Nuel (7, 8) , Violaine Planté-Bordeneuve (2)

1 IMRB - Institut Mondor de Recherche Biomédicale
2 Service de neurologie [Mondor]
3 MAP5 - UMR 8145 - Mathématiques Appliquées Paris 5
4 UMR_S 669 - Troubles du comportement alimentaire de l'adolescent
5 INSERM U955, équipe 11
6 U894 - Centre de Psychiatrie et Neurosciences
7 LPMA - Laboratoire de Probabilités et Modèles Aléatoires
8 IMJ-PRG (UMR_7586) - Institut de Mathématiques de Jussieu - Paris Rive Gauche

Significant variability of phenotype and age of onset are well known in TTR-FAP associated to a wide spectrum of pathogenic TTR variants, among which Val30Met is the most frequent [1,2]. Recently, new therapeutic options became available that should be administered from the very onset of symptoms. In this context, the knowledge of the risk of being symptomatic for mutation carriers (penetrance) is essential to adjust the follow-up of carriers and for patient management [3,4]. This study aims to refine penetrance estimates in the main pathogenic variants encountered in our TTR-FAP population using a newly developed non parametric approach named NPSE for Non-Parametric Survival Estimate.

Domaines: Santé publique et épidémiologie; Génétique humaine

Farida Gorram, Flora Alarcon, Hervé Perdry, Bérénice Hébrard, Thibaud Damy, et al.. Refine penetrance estimates in the main pathogenic variants of transthyretin hereditary (familial) amyloid polyneuropathy (TTR-FAP) using a new non-parametric approach (NPSE). Amyloid: The Journal of Protein Folding Disorders, 2017, PROCEEDINGS OF THE XVth INTERNATIONAL SYMPOSIUM ON AMYLOIDOSIS, 24 (Supp 1), pp.115-116. ⟨10.1080/13506129.2017.1293515⟩. ⟨hal-01539752⟩