Integrating D4Z4 methylation analysis into clinical practice: improvement of FSHD molecular diagnosis through distinct thresholds for 4qA/4qA and 4qA/4qB patients.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Strafella Claudia, Megalizzi Domenica, Trastulli Giulia, Proietti Piorgo Emma, Colantoni Luca, Tasca Giorgio, Monforte Mauro, Zampatti Stefania, Primiano Guido, Sancricca Cristina, Bortolani Sara, Torchia Eleonora, Ravera Beatrice, Torri Francesca, Gadaleta Giulio, Risi Barbara, Caria Filomena, Gerardi Francesca, Carraro Elena, Gioiosa Valeria, Garibaldi Matteo, Tufano Laura, Frezza Erica, Massa Roberto, Caltagirone Carlo, Pennisi Elena Maria, Petrucci Antonio, Pane Marika, Frongia Annalia, Gragnani Francesca, Scutifero Marianna, Mandich Paola, Grandis Marina, Maioli Maria Antonietta, Casali Carlo, Manfroi Elisabetta, Politano Luisa, Passamano Luigia, Petillo Roberta, Rodolico Carmelo, Pugliese Alessia, Previtali Stefano Carlo, Sansone Valeria, Vercelli Liliana, Mongini Tiziana Enrica, Ricci Giulia, Siciliano Gabriele, Filosto Massimiliano, Ricci Enzo, Cascella Raffaella, Giardina Emiliano, FSHD Italian Clinical Group
Аннотация
RESULTS: Among the 218 subjects, the 4q variant type distribution was 54% 4qA/4qA, 43% 4qA/4qB and 3% 4qB/4qB. The methylation analysis was performed only on carriers of at least one 4qA allele. After refining the classification threshold, the test reached the following performance metrics: sensitivity = 0.90, specificity = 1.00 and accuracy = 0.93. These results confirmed the effectiveness of the methylation assay in identifying patients with genetic signature compatible with FSHD1 and FSHD2 based on their DUX4-PAS and DR1 profile, respectively. The methylation data were also evaluated with respect to the clinical information.
CONCLUSIONS: The study confirmed the ability of the method to accurately identify methylation profiles compatible with FSHD genetic signatures considering the 4q genotype. Moreover, the test allows the detection of hypomethylated profiles in asymptomatic patients, suggesting its potential application in identifying preclinical conditions in patients with positive family history and FSHD genetic signatures. Furthermore, the present work emphasizes the importance of interpreting methylation profiles considering the patients' clinical data.