[Deficiency of human ciliary neurotropic factor (CNTF) is not causally related to amyotrophic lateral sclerosis...

Ciliary neurotrophic factor (CNTF) promotes the survival of motor neurons in vitro and in vivo. A recent report showed that disruption of the CNTF gene in mice caused motor neuron degeneration. We have found a null mutation in the human CNTF gene. The mutated allele shows a G to A transition producing a new splice acceptor site and the resulting mRNA species codes for an aberrant protein. Analysis of tissue samples demonstrated that the mutated allele expressed only the mutated mRNA species. In 391 Japanese people tested, 61.9% were normal homozygotes, 35.8% heterozygotes and 2.3% mutant homozygotes. The distribution of the three genotypes is similar in healthy and neurological disease subjects including ALS patients. Our findings indicate that CNTF deficiency is not causally related to ALS.