Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX

Mutations in the Senataxin gene (SETX) are associated with autosomal recessive ataxia-ocular apraxia 2 (AOA2) and autosomal dominant juvenile ALS (ALS4). Here, the authors describe novel homozygous missense mutations in SETX, M274I, and R1294C, found in two siblings with ataxia, peripheral neuropathy, and increased serum alpha-fetoprotein level and three other siblings with heterozygous missense mutations who were neurologically asymptomatic. The results demonstrate that the double missense mutations are responsible for AOA2 but not for ALS4.