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Association of a Null Mutation in the CNTF Gene With Early Onset of Multiple Sclerosis
Ralf Giess, MD;
Mathias Mäurer, MD;
Ralf Linker, MD;
Ralf Gold, MD;
Monika Warmuth-Metz, MD;
Klaus V. Toyka, MD;
Michael Sendtner, MD;
Peter Rieckmann, MD
Arch Neurol. 2002;59:407-409.
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.
Subjects and 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.
From the Division of Neuroradiology (Dr Warmuth-Metz), Department of
Neurology (Drs Giess, Mäurer, Linker, Gold, Toyka, and Rieckmann), and
Institute of Clinical Neurobiology (Dr Sendtner), Bayerische Julius-Maximilians
Universität, Würzburg, Germany.
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