The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor.
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.
Bernal
S
S
Alías
L
L
Barceló
M J
MJ
Also-Rallo
E
E
Martínez-Hernández
R
R
Gámez
J
J
Guillén-Navarro
E
E
Rosell
J
J
Hernando
I
I
Rodríguez-Alvarez
F J
FJ
Borrego
S
S
Millán
J M
JM
Hernández-Chico
C
C
Baiget
M
M
Fuentes-Prior
P
P
Tizzano
E F
EF
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*
D055540:Survival of Motor Neuron 2 Protein