INVESTIGATION OF A NULL MUTATION OF THE CNTF GENE IN FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS

Neurotrophic factors, such as ciliary neurotrophic factor (CNTF), have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), a human neurodegenerative disease primarily of upper and lower motor neurones. A null mutation of the CNTF gene has recently been des cribed. The mutation is an intronic point mutation (G to A) which gene rates a new splice acceptor site and a 4 bp insertion within the CNTF coding region, and prevents the expression of the normal protein. We i nvestigated this as a candidate gene in 49 families with ALS, where th e genetic component may be expected to be strongest. 65% were normal h omozygotes, and 35% were heterozygotes for the mutation. No mutant hom ozygotes were detected. The absence of CNTF protein expression associa ted with the homozygote mutation does not appear to be of major signif icance in the development of ALS.