CNTF Null alleles are not enriched in ALS and CMT patients

Joost van Wijk, Ted Bradley, J.M.B. Vianney de Jong, Paul van Vught, Marja Jakobs, Leonard van den Berg and Frank Baas

Neurogenetics, AMC, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands and Neurology, UMCU, Utrecht, The Netherlands

Ciliary neurotrophic factor (CNTF) plays an important role in neurone survival. Both in vitro and in vivo experiments suggest that lack of CNTF may affect (motor)neuron survival. CNTF can alleviate the phenotype of the pmn mice. In addition CNTF has been suggested to be a modifier of FALS (Giess et al 2002). CNTF expression is down regulated in brain of ALS cases and in the PNS of models for Charcot-Marie-Tooth disease.

A homozygous splice site mutation in intron 1 of the CNTF gene occurs in about 2% of the population. People with this mutation show no obvious phenotype, but in view of the association of this mutation with early onset FALS we performed a large study for this CNTF mutation in ALS and CMT cases.