Practical guidelines to manage discordant situations of SMN2 copy number in patients with spinal muscular atrophy
Cusco, Ivon (Hospital Universitari Vall d'Hebron)
Bernal, Sara (Institut d'Investigació Biomèdica Sant Pau)
Blasco-Pérez, Laura (Hospital Universitari Vall d'Hebron)
Calucho, Maite (Hospital Universitari Vall d'Hebron)
Alías, Laura (Hospital Universitari Vall d'Hebron)
Fuentes-Prior, Pablo (Institut d'Investigació Biomèdica Sant Pau)
Tizzano, Eduardo F (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	Objective Assessment of SMN2 copy number in patients with spinal muscular atrophy (SMA) is essential to establish careful genotype-phenotype correlations and predict disease evolution. This issue is becoming crucial in the present scenario of therapeutic advances with the perspective of SMA neonatal screening and early diagnosis to initiate treatment, as this value is critical to stratify patients for clinical trials and to define those eligible to receive medication. Several technical pitfalls and interindividual variations may account for reported discrepancies in the estimation of SMN2 copy number and establishment of phenotype-genotype correlations. Methods We propose a management guide based on a sequence of specified actions once SMN2 copy number is determined for a given patient. Regardless of the method used to estimate the number of SMN2 copies, our approach focuses on the manifestations of the patient to recommend how to proceed in each case. Results We defined situations according to SMN2 copy number in a presymptomatic scenario of screening, in which we predict the possible evolution, and when a symptomatic patient is genetically confirmed. Unexpected discordant cases include patients having a single SMN2 copy but noncongenital disease forms, 2 SMN2 copies compatible with type II or III SMA, and 3 or 4 copies of the gene showing more severe disease than expected. Conclusions Our proposed guideline would help to systematically identify discordant SMA cases that warrant further genetic investigation. The SMN2 gene, as the main modifier of SMA phenotype, deserves a more in-depth study to provide more accurate genotype-phenotype correlations.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Neurology: Genetics, Vol. 6 Núm. 6 (2020) , p. e530, ISSN 2376-7839

DOI: 10.1212/NXG.0000000000000530
PMID: 33324756

10 p, 279.9 KB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut de Recerca Sant Pau
Artículos > Artículos de investigación
Artículos > Artículos publicados