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

Spinal muscular atrophy (SMA) is due to the homozygous absence of 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-mod...

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Bibliographic Details
Published in:	Journal of medical genetics Vol. 60; no. 7; p. 697
Main Authors:	Abiusi, Emanuela, Vaisfeld, Alessandro, Fiori, Stefania, Novelli, Agnese, Spartano, Serena, Faggiano, Maria Vittoria, Giovanniello, Teresa, Angeloni, Antonio, Vento, Giovanni, Santoloci, Roberta, Gigli, Francesca, D'Amico, Adele, Costa, Simonetta, Porzi, Alessia, Panella, Mara, Ticci, Chiara, Daniotti, Marta, Sacchini, Michele, Boschi, Ilaria, Dani, Carlo, Agostiniani, Rino, Bertini, Enrico, Lanzone, Antonio, Lamarca, Giancarlo, Genuardi, Maurizio, Pane, Marika, Donati, Maria Alice, Mercuri, Eugenio, Tiziano, Francesco Danilo
Format:	Journal Article
Language:	English
Published:	England 01-07-2023
Subjects:	Genotype Humans Infant, Newborn Italy Muscular Atrophy, Spinal - diagnosis Muscular Atrophy, Spinal - genetics Neonatal Screening - methods Pilot Projects Italy Genetics, Population Genetic Testing Neonatal Screening Neuromuscular Diseases
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Summary:	Spinal muscular atrophy (SMA) is due to the homozygous absence of 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. The screening test was performed by an in-house-developed qPCR assay, amplifying and . Molecular prognosis was assessed on fresh blood samples. We found 15 patients/90885 newborns (incidence 1:6059) having the following 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. 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; copy assessment needs to be standardised; commercially available tests need to be improved for higher copies determination; and the splicing-modifier variants should be routinely tested in SMA-NBS.
ISSN:	1468-6244
DOI:	10.1136/jmg-2022-108873