Dystonia

INDEX

Heterozygous mutations in the GNAL gene (guanine nucleotide-binding protein subunit alpha L) encoding the stimulatory α subunit of the heterotrimeric G protein G olf cause cervical or cranial dystonia with a mean onset in the thirties. About 30 different GNAL mutations have been reported in dystonia patients, including missense mutations and nonsense variants.

GNAL mutations seem to be highly but not fully penetrant. A homozygous GNAL missense mutation (p.R329W) was found in siblings with childhood-onset generalized dystonia and mild intellectual disability: biallelic mutations in GNAL may therefore occur but appear to cause a more severe phenotype.