Background: The F64L variant is among the most frequent TTR mutations in Italy, typically associated with a predominantly neurologic phenotype and limited cardiac involvement. Methods: Data from 181 ATTRv patients in the multicenter Patisiranitaly database treated with Patisiran since 2020 were analyzed. Neurologic impairment scores, Norfolk QoL-DN, and cardiac parameters were compared between F64L (n = 56), V30M (n = 37), and non-F64L (n = 125) patients at baseline and during follow-up. Cluster analysis was applied to identify patient subgroups based on these variables. Results: F64L represented 30.9% of the cohort. Compared to non-F64L patients, F64L patients had a higher prevalence of neurologic onset and neurologic phenotype, a thinner interventricular septum, and lower NT-proBNP levels. Cluster analysis segregated patients into two distinct groups, predominantly reflecting F64L vs. non-F64L status and corresponding neurologic severity. F64L patients showed milder cardiac involvement compared to V30M patients. Longitudinal repeated-measures ANOVA showed stable clinical and instrumental measures. Conclusions: F64L is characterized by predominant neurologic involvement and milder cardiac involvement in this Patisiran-treated cohort. Mutation-specific diagnostic and follow-up strategies are essential to capture its natural history and treatment response.
Deep Phenotyping of F64L Mutation in a Multicentric Cohort of Patisiran‐Treated Hereditary Transthyretin Amyloidosis Patients (Patisiranitaly) / Ceccanti, M., Guaraldi, P., Romano, A., Antonini, G., Barilaro, A., Briani, C., Burattini, M., Gianoli, M., Carlini, G., Cianci, V., Dossi, M.C., Di Lisi, D., Di Muzio, A., Ratti, A., Filosto, M., Gasverde, S., Gemelli, C., Gentile, L., Goglia, M., Leonardi, L., et al.. - In: EUROPEAN JOURNAL OF NEUROLOGY. - ISSN 1351-5101. - 33:6(2026). [10.1111/ene.70657]
Deep Phenotyping of F64L Mutation in a Multicentric Cohort of Patisiran‐Treated Hereditary Transthyretin Amyloidosis Patients (Patisiranitaly)
Manganelli, Fiore;Palumbo, Giovanni;Tozza, Stefano;Castiglia, Mariagiovanna;
2026
Abstract
Background: The F64L variant is among the most frequent TTR mutations in Italy, typically associated with a predominantly neurologic phenotype and limited cardiac involvement. Methods: Data from 181 ATTRv patients in the multicenter Patisiranitaly database treated with Patisiran since 2020 were analyzed. Neurologic impairment scores, Norfolk QoL-DN, and cardiac parameters were compared between F64L (n = 56), V30M (n = 37), and non-F64L (n = 125) patients at baseline and during follow-up. Cluster analysis was applied to identify patient subgroups based on these variables. Results: F64L represented 30.9% of the cohort. Compared to non-F64L patients, F64L patients had a higher prevalence of neurologic onset and neurologic phenotype, a thinner interventricular septum, and lower NT-proBNP levels. Cluster analysis segregated patients into two distinct groups, predominantly reflecting F64L vs. non-F64L status and corresponding neurologic severity. F64L patients showed milder cardiac involvement compared to V30M patients. Longitudinal repeated-measures ANOVA showed stable clinical and instrumental measures. Conclusions: F64L is characterized by predominant neurologic involvement and milder cardiac involvement in this Patisiran-treated cohort. Mutation-specific diagnostic and follow-up strategies are essential to capture its natural history and treatment response.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
