Among the dozen known mutations in the PrP gene which segregate with the inherited prion diseases, only 2 mutations have been described in Israel so far: the codon 200 mutation in Creutzfeldt-Jakob disease (CJD) affected Libyan Jews, and the codon 102 mutation in 1 Jewish Gerstmann-Straussler-Scheinker (GSS) affected pedigree of German origin. We report here 2 unrelated CJD178 cases affected by a unique phenotype: aphemia, apraxia, uncontrolled laugh and no ataxia. As opposed to other CJD178 patients, in these patients, the signal transduction protein 14-3-3, recently suggested as a CJD marker, was detected in the cerebrospinal fluid samples by immunostaining. The D178N mutation, known to be linked to 2 different phenotypes: Fatal Familial Insomnia (FFI) and CJD, was not described so far among Jews. The phenotype reported here, although it shares a common Va1129/Asn178 haplotype with the previously described CJD178, may point to a different clinical subtype of CJD178.