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


Por: Bernal, S, Alias, L, Barcelo, MJ, Also-Rallo, E, Martinez-Hernandez, R, Gamez, J, Guillen-Navarro, E, Rosell, J, Hernando, I, Rodriguez-Alvarez, FJ, Borrego, S, Millan, JM, Hernandez-Chico, C, Baiget, M, Fuentes-Prior, P, Tizzano, EF

Publicada: 1 sep 2010
Resumen:
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.

Filiaciones:
Bernal, S:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain

Alias, L:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain

Barcelo, MJ:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain

Also-Rallo, E:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain

Martinez-Hernandez, R:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain

Gamez, J:
 Hosp Gen Valle Hebron, Serv Neurol, Barcelona, Spain

Guillen-Navarro, E:
 Hosp Univ Virgen Arrixaca, Unidad Genet Med, Murcia, Spain

Rosell, J:
 Hosp Son Dureta, Dept Genet, Palma de Mallorca, Spain

Hernando, I:
 Univ Asturias, Serv Genet Hosp, Oviedo, Spain

Rodriguez-Alvarez, FJ:
 Hosp Ramon & Cajal, Unidad Genet, E-28034 Madrid, Spain

 CIBERER, U728, Madrid, Spain

Borrego, S:
 Hosp Virgen Rocio, Unidad Gest Clin Genet Reprod Med Fetal, Seville, Spain

 CIBERER, U702, Seville, Spain

Millan, JM:
 Hosp La Fe, Unidad Genet, Valencia, Spain

 CIBERER, Valencia, Spain

Hernandez-Chico, C:
 Hosp Ramon & Cajal, Unidad Genet, E-28034 Madrid, Spain

 CIBERER, U728, Madrid, Spain

Baiget, M:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain

Fuentes-Prior, P:
 Hosp Santa Creu & Sant Pau, Unitat Bases Mol Malalties, Res Inst, Barcelona, Spain

Tizzano, EF:
 Hosp Santa Creu & Sant Pau, Serv Genet, Barcelona 08025, Spain

 CIBERER, U705, Barcelona, Spain
ISSN: 00222593
Editorial
BMJ PUBLISHING GROUP, BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 47 Número: 9
Páginas: 640-642
WOS Id: 000283084000011
ID de PubMed: 20577007
imagen Open Access

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