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

Autores de IIS La Fe

• 

  José María Millán Salvador

  Autor

Participantes ajenos a IIS La Fe

• Bernal S
• Alías L
• Barceló MJ
• Also-Rallo E
• Martínez-Hernández R
• Gámez J
• Guillén-Navarro E
• Rosell J
• Hernando I
• Rodríguez-Alvarez FJ
• Borrego S
• Hernández-Chico C
• Baiget M
• Fuentes-Prior P
• Tizzano EF

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.