The role of hereditary spastic paraplegia related genes in multiple sclerosis : A study of disease susceptibility and clinical outcome

• Published in: Journal of neurology Vol. 254; no. 9; pp. 1221 - 1226
• Main Authors: DELUCA, G. C, RAMAGOPALAN, S. V, EBERS, G. C, CADER, M. Z, DYMENT, D. A, HERRERA, B. M, ORTON, S, DEGENHARDT, A, PUGLIATTI, M, SADOVNICK, A. D, SOTGIU, S
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-09-2007; Springer Nature B.V
• Subjects: Adenosine Triphosphatases - genetics; Adult; Biological and medical sciences; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disability Evaluation; Disease Progression; Female; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Medical sciences; Multiple Sclerosis - diagnosis; Multiple Sclerosis - genetics; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Polymorphism, Single Nucleotide; Prognosis; Spastic Paraplegia, Hereditary - genetics; Spastin; Hereditary spastic paraplegia; Multiple sclerosis; Nervous system diseases; Prognosis; genetics; Drug susceptibility test; Central nervous system disease; Degenerative disease; Spinal cord disease; Cerebral disorder; Genetic disease; Inflammatory disease
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-006-0505-4

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system unsurpassed for its variability in disease outcome. It has been observed that axonal loss in MS is significant and that irreversible clinical disability relates to such axonal loss. The clinical similarities between Hereditary Spastic Paraplegia (HSP) and progressive MS, along with their analogous profiles of axonal loss in the long tracts, make the genes known to cause HSP biologically relevant candidates for the study of clinical outcome in MS. A cohort of sporadic MS cases and a set of unaffected controls were used to determine the role of HSP genes on MS susceptibility and disease severity. The MS cases were taken from opposite extremes of the putative distribution of long-term outcome using the most stringent clinical criteria to date. Genotyping the two sets of MS patients and controls could not provide any evidence to suggest that genes involved in the pathogenesis of HSP (Paraplegin, NIPA1, KIF5A, HSPD1, Atlastin, Spartin, Spastin, PLP1, L1CAM, Maspardin and BSCL2) play a role in susceptibility to, or modifying the course of, MS, although small effects of these genes cannot be ruled out.