The SLC18A3 gene encodes for the vesicular acetylcholine transporter (VAChT), which is the only VAChT isoform in mammals and is required for acetylcholine release at the neuromuscular junction and in the central nervous system.
The severity of SLC18A3-associated disease is highly variable. The most severe phenotype (i.e., fetal akinesia deformation sequence, FADS) has been associated with homozygous nonsense mutations. It can be speculated that complete absence of protein function leads to FADS, whereas reduced protein activity leads to congenital myasthenic syndrome. Of the reported patients with congenital myasthenic syndrome (CMS) one patient was compound heterozygous for a gross deletion and a missense mutation. All other CMS patients reported by 2021 harbor missense mutations. More information is needed on the genotype-phenotype correlations of SLC18A3 missense mutations.
Diagnosis may be reached using gene panels (if the SLC18A3 gene is included in the panel) or exome sequencing.
SLC18A3