The c.859G>C variant in the SMN2 gene is associated with both type II and III SMA and originates from a common ancestor

Sara Bernal (1) , Laura Alías (1) , Maria Jesus Barceló (1) , Eva Also-Rallo (1) , Rebeca Martínez-Hernández (1) , Josep Gámez (2) , Encarnación Guillén (3) , Jordi Rosell (4) , Inés Hernando (5) , Francisco J Rodríguez-Alvarez (6) , Salud Borrego (7) , José María Millán (8) , Concepción Hernández-Chico (6) , Montserrat Baiget (1) , Pablo Fuentes-Prior (9) , Eduardo F Tizzano (1)

1 Hospital de la Santa Creu i Sant Pau
2 Vall d'Hebron University Hospital [Barcelona]
3 Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia]
4 Hospital Son Dureta, Palma de Mallorca
5 Hospital Universitario de Asturias, Oviedo
6 Hospital Universitario Ramón y Cajal [Madrid]
7 Hospital Universitario Virgen del Rocío [Sevilla]
8 Hospital La Fe, and CIBERER, Valencia
9 Research Institute, Hospital de la Santa Creu i Sant Pau , Barcelona

Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA).1 A highly similar centromeric gene (SMN2) can only partially compensate for SMN1 deficiency. The c.859G>C variant in SMN2, has been recently reported as a positive disease modifier.2,3 We identified the variant in 10 unrelated chronic SMA patients with a wide spectrum of phenotypes ranging from type II patients who can only sit to adult walkers. Haplotye analysis strongly suggests that the variant originated from a common ancestor. Our results confirm that the c.859G>C variant is a milder SMN2 allele and predict a direct correlation between SMN activity and phenotypic severity.

Mots clés: Clinical genetics; Molecular genetics; Neurology; Motor neurone disease; Neuromuscular disease

Sara Bernal, Laura Alías, Maria Jesus Barceló, Eva Also-Rallo, Rebeca Martínez-Hernández, et al.. The c.859G>C variant in the SMN2 gene is associated with both type II and III SMA and originates from a common ancestor. Journal of Medical Genetics, 2010, 47 (9), pp.640. ⟨10.1136/jmg.2010.079004⟩. ⟨hal-00557399⟩