@article {Abiusijmg-2022-108873, author = {Emanuela Abiusi and Alessandro Vaisfeld and Stefania Fiori and Agnese Novelli and Serena Spartano and Maria Vittoria Faggiano and Teresa Giovanniello and Antonio Angeloni and Giovanni Vento and Roberta Santoloci and Francesca Gigli and Adele D{\textquoteright}Amico and Simonetta Costa and Alessia Porzi and Mara Panella and Chiara Ticci and Marta Daniotti and Michele Sacchini and Ilaria Boschi and Enrico Bertini and Antonio Lanzone and Giancarlo Lamarca and Maurizio Genuardi and Marika Pane and Maria Alice Donati and Eugenio Mercuri and Francesco Danilo Tiziano}, editor = {, and , and Accardo, Maria and Gambi, Beatrice and Agostiniani, Rino and Giampaoli, Simonetta and Ahmed, Ubah Farah and Giannini, Carlo and Alecci, Concetta and Giardini, Valerio and Amendolea, Antonella and Guarguagli, Monica and Bartolucci, Monica and Haass, Cristina and Belisario, Ivana and Innocenti, Isabella and Belluomini, Paola and Innocenti Berti, Maria Cristina and Bernardini, Claudia and Maggi, Claudia and Bernardini, Roberto and Magi, Letizia and Bert{\`o}, Luisa and Malorgio, Roccuccia and Bini, Rita and Maragliano, Giovanna and Bolgia, Leonardo and Maraglino, Vita and Boscioni, Mario and Marotta, Anna and Bracaglia, Giorgio and Martini, Cristina and Brachini, Elisa and Martufi, Palmina and Bruschi, Elisa and Mastropasqua, Stefania and Campa, Monica and Matera, Maria Rosaria and Caprilli, Monica and Memmini, Graziano and Carcione, Simona and Mendicino, Angela and Cardiello, Angelo and Mercurio, Sabrina and Cartolano, Francesco and Meucci, Alessandra and Casati, Alessandra and Milita, Osvaldo and Ceccarelli, Sandra and Morano, Zeudi and Chiellini, Marzia and Nardi, Eleonora and Ciccotti, Rossella and Novelli, Sandra and Cioli, Elena and Padovano, Luigi and Civitelli, Flavio and Palermo, Maria Gabriella and Colella, Maria Giovanna and Pascucci, Serena and Coppotelli, Luigina and Patrizia, Caterini and Crescenzi, Francesco and Percoco, Assunta and Dani, Carlo and Petrolati, Stefania and Danieli, Roberto and Pitaro, Rosanna and Angelis, Tamara De and Raponi, Marilena and Martinis, Mauro De and Riccobene, Francesco and degl{\textquoteright}Innocenti, Elena and Rosa, Giovanni and Sette, Laura Del and Roversi, Amanda and Paolo, Ambrogio Di and Sadocco, Sabrina and Ruzza, Luigi Di and Santarelli, Emanuela and Silvio, Rosalia Di and Tafi, Luca and Francesco, Dituri and Tomasini, Barbara and Egho, Gwenna and Traupe, Martha and Emili, Daniela and Vaccaro, Angelina and Filippo, Luca and Vasarri, Pierluigi and Foglia, Claudia and Ventura, Valentina and Gabriellini, Francesco and Vitale, Stefano and Gagliardi, Luigi and Zingoni, Anna Maria and Gallo, Annamaria}, title = {Experience of a 2-year spinal muscular atrophy NBS pilot study in Italy: towards specific guidelines and standard operating procedures for the molecular diagnosis}, elocation-id = {jmg-2022-108873}, year = {2022}, doi = {10.1136/jmg-2022-108873}, publisher = {BMJ Publishing Group Ltd}, abstract = {Background Spinal muscular atrophy (SMA) is due to the homozygous absence of SMN1 in around 97\% of patients, independent of the severity (classically ranked into types I{\textendash}III). The high genetic homogeneity, coupled with the excellent results of presymptomatic treatments of patients with each of the three disease-modifying therapies available, makes SMA one of the golden candidates to genetic newborn screening (NBS) (SMA-NBS). The implementation of SMA in NBS national programmes occurring in some countries is an arising new issue that the scientific community has to address. We report here the results of the first Italian SMA-NBS project and provide some proposals for updating the current molecular diagnostic scenario.Methods The screening test was performed by an in-house-developed qPCR assay, amplifying SMN1 and SMN2. Molecular prognosis was assessed on fresh blood samples.Results We found 15 patients/90885 newborns (incidence 1:6059) having the following SMN2 genotypes: 1 (one patient), 2 (eight patients), 2+c.859G\>C variant (one patient), 3 (three patients), 4 (one patient) or 6 copies (one patient). Six patients (40\%) showed signs suggestive of SMA at birth. We also discuss some unusual cases we found.Conclusion The molecular diagnosis of SMA needs to adapt to the new era of the disease with specific guidelines and standard operating procedures. In detail, SMA diagnosis should be felt as a true medical urgency due to therapeutic implications; SMN2 copy assessment needs to be standardised; commercially available tests need to be improved for higher SMN2 copies determination; and the SMN2 splicing-modifier variants should be routinely tested in SMA-NBS.Data sharing not applicable as no datasets generated and/or analysed for this study.}, issn = {0022-2593}, URL = {https://jmg.bmj.com/content/early/2022/11/22/jmg-2022-108873}, eprint = {https://jmg.bmj.com/content/early/2022/11/22/jmg-2022-108873.full.pdf}, journal = {Journal of Medical Genetics} }