Homozygous <i>GNAL</i> mutation associated with familial childhood-onset generalized dystonia

Abstract

Heterozygous loss-of-function mutations in the GNAL gene encoding the α subunit of the heterotrimeric G protein Golf (Gαolf) are known to cause isolated dystonia.1,2 Gαolf is enriched in the striatum where it couples D1 dopamine (D1R) and A2A adenosine (A2AR) receptors to the activation of adenylyl cyclase type 5 (AC5). Mutations in ADCY5 , the gene encoding AC5, are also known to lead to chorea and dystonia.3,4 Previous functional studies of mutated Gαolf variants have revealed deficiencies in activation after D1R stimulation.1,5 Acknowledgment: The authors thank the patients and their family for their participation; without their support, this work would not have been possible.