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The c.859G>C variant in the SMN2 gene is associated with types II and III SMA and originates from a common ancestor
  1. S Bernal1,
  2. L Alías1,
  3. M J Barceló1,
  4. E Also-Rallo1,
  5. R Martínez-Hernández1,
  6. J Gámez2,
  7. E Guillén-Navarro3,
  8. J Rosell4,
  9. I Hernando5,
  10. F J Rodríguez-Alvarez6,
  11. S Borrego7,
  12. J M Millán8,
  13. C Hernández-Chico6,
  14. M Baiget1,
  15. P Fuentes-Prior9,
  16. E F Tizzano1
  1. 1Servei de Genètica, Hospital de la Santa Creu i Sant Pau, and CIBERER U-705, Barcelona, Spain
  2. 2Servei de Neurología, Hospital Vall d'Hebron, Barcelona, Spain
  3. 3Unidad de Genética Médica, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain
  4. 4Departamento de Genética, Hospital Son Dureta, Palma de Mallorca, Spain
  5. 5Servicio de Genética, Hospital Universitario de Asturias, Oviedo, Spain
  6. 6Unidad de Genética, Hospital Ramón y Cajal, and CIBERER U-728, Madrid, Spain
  7. 7Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Hospital Virgen del Rocío and CIBERER U-702, Sevilla, Spain
  8. 8Unidad de Genética, Hospital La Fe, and CIBERER, Valencia, Spain
  9. 9Unitat Bases Moleculars de les Malalties, Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  1. Correspondence to Eduardo F Tizzano, Genetics, Hospital de la Santa Creu i Sant Pau, Sant Antoni Ma. Claret 167, 08025 Barcelona, Spain; etizzano{at}santpau.cat

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.

  • Clinical genetics
  • molecular genetics
  • neurology
  • motor neurone disease
  • neuromuscular disease

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Footnotes

  • Funding Other funders: GENAME Project, CIBERER Intramural U-705 and FIS08-0729.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Hospital Santa Creu i Sant Pau, Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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