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 described. The mutation is an intronic point mutation (G to A) which generates a new splice acceptor site and a 4 bp insertion within the CNTF coding region, and prevents the expression of the normal protein. We investigated this as a candidate gene in 49 families with ALS, where the genetic component may be expected to be strongest. 65% were normal homozygotes, and 35% were heterozygotes for the mutation. No mutant homozygotes were detected. The absence of CNTF protein expression associated with the homozygote mutation does not appear to be of major significance in the development of ALS.