Association of a null mutation in the CNTF gene with early onset of multiple sclerosis.
BACKGROUND
Immune-mediated demyelination and axonal damage lead to early functional impairment in multiple sclerosis (MS). Ciliary neurotrophic factor (CNTF) is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks.


METHODS
We screened 288 unselected patients with multiple sclerosis (MS) (mean age, 40.2 +/- 10.2 years; range, 18-71 years) for a previously described homozygous null mutation within the CNTF gene leading to a truncated, biologically inactive protein. The G-to-A CNTF null mutation at position -6 of the second exon was identified by a HaeIII polymorphism of the polymerase chain reaction-amplified genomic DNA.


RESULTS
The homozygous CNTF null mutation (CNTF -/-) was found in 7 (2.4%) of the 288 randomly selected patients with MS. Patients with the CNTF -/- genotype had a significantly earlier onset of disease (17 vs 27 years; Mann-Whitney test, P =.007) with predominant motor symptoms.


CONCLUSIONS
These results suggest that CNTF contributes to time and site of early clinical manifestation. The frequency of patients with MS with a homozygous CNTF null mutation in this population was not higher than in control groups, indicating that the CNTF null mutation is not a risk factor for development of MS.
Giess
Ralf
R
Department of Neurology, University of Würzburg, Josef Schneider Strasse 11, D-97080 Würzburg, Germany.
Mäurer
Mathias
M
Linker
Ralf
R
Gold
Ralf
R
Warmuth-Metz
Monika
M
Toyka
Klaus V
KV
Sendtner
Michael
M
Rieckmann
Peter
P
D000328:Adult; D017668:Age of Onset; D000368:Aged; D020934:Ciliary Neurotrophic Factor / Q000235:genetics*; D004185:Disability Evaluation; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000503:physiopathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000502:physiology*
D020934:Ciliary Neurotrophic Factor