Experience of a 2-year spinal muscular atrophy NBS pilot study in Italy: Towards specific guidelines and standard operating procedures for the molecular diagnosis

Emanuela Abiusi, Alessandro Vaisfeld, Simona Fiori, Agnese Novelli, Serena Spartano, Maria Vittoria Faggiano, Teresa Giovanniello, Antonio Angeloni, Giovanni Vento, Roberta Santoloci, Francesca Gigli, Adele D'Amico, Simonetta Costa, Alessia Porzi, Mara Panella, Chiara Ticci, Marta Daniotti, Michele Sacchini, Ilaria Boschi, Carlo DaniRino Agostiniani, Enrico Bertini, Enrico Silvio Bertini, Antonio Lanzone, Giancarlo Lamarca, Maurizio Genuardi, Marika Pane, Marika Pane, Maria Alice Donati, Eugenio Maria Mercuri, Francesco Danilo Tiziano

Research output: Contribution to journalArticle


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-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.
Original languageEnglish
Pages (from-to)697-705
Number of pages9
JournalJournal of Medical Genetics
Publication statusPublished - 2023


  • Genetic Testing
  • Neuromuscular Diseases
  • Neonatal Screening
  • Genetics, Population


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