title: The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor.
abstract: Homozygous mutations of the telomeric SMN1 gene lead to degeneration of motor neurons causing spinal muscular atrophy (SMA). 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. 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. Haplotype 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.
authors.forename: S
authors.initials: S
authors.lastname: Bernal
authors.forename: L
authors.initials: L
authors.lastname: Alías
authors.forename: M J
authors.initials: MJ
authors.lastname: Barceló
authors.forename: E
authors.initials: E
authors.lastname: Also-Rallo
authors.forename: R
authors.initials: R
authors.lastname: Martínez-Hernández
authors.forename: J
authors.initials: J
authors.lastname: Gámez
authors.forename: E
authors.initials: E
authors.lastname: Guillén-Navarro
authors.forename: J
authors.initials: J
authors.lastname: Rosell
authors.forename: I
authors.initials: I
authors.lastname: Hernando
authors.forename: F J
authors.initials: FJ
authors.lastname: Rodríguez-Alvarez
authors.forename: S
authors.initials: S
authors.lastname: Borrego
authors.forename: J M
authors.initials: JM
authors.lastname: Millán
authors.forename: C
authors.initials: C
authors.lastname: Hernández-Chico
authors.forename: M
authors.initials: M
authors.lastname: Baiget
authors.forename: P
authors.initials: P
authors.lastname: Fuentes-Prior
authors.forename: E F
authors.initials: EF
authors.lastname: Tizzano
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009134:Muscular Atrophy, Spinal / Q000145:classification* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D013030:Spain; D055540:Survival of Motor Neuron 2 Protein / Q000145:classification / Q000235:genetics*
chemical_list: D055540:Survival of Motor Neuron 2 Protein