The dopamine<unk>  protein, pictured here, is mutated in DTDS patients. DTDS is caused by mutations in the SLC6A3 gene, which codes for the dopamine<unk>  protein DAT. In contrast to various mutations that up-regulate DAT activity, which is implicated in clinical depression, this mutation results in DAT down-regulation and, consequently, DTDS. Known DTDS-related SLC6A3 mutations include: * R85L * A314V * G386R * R445C * Y470S In vitro replication of SLC6A3 mutations like those present in DTDS demonstrate multifaceted loss of dopamine<unk>  functions. Dopamine intake is universally impaired. These mutants also demonstrated diminished dopamine binding affinity, reduced cell surface<unk> , loss of post-translational dopamine<unk>  glycosylation, and failure of amphetamine-mediated dopamine efflux. The age at which signs and symptoms appear seems to be related to the severity of DAT dysfunction. Early-onset DTDS movement problems in infancy most often have<unk>  activity that is less than 5 percent of normal. Those whose movement problems appear in childhood or later tend to have somewhat higher levels of<unk>  activity, although they are still lower than normal. Researchers speculate that higher levels of<unk>  activity may delay the onset of the disease in these individuals. DTDS is inherited in an autosomal recessive pattern, which means, for affected individuals, both copies of the gene in each cell have SLC6A3 mutations. As such, each sibling of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and 25% chance of being unaffected and not a carrier. Once a SLC6A3 pathogenic variant is identified within an affected family member, carrier testing for at-risk relatives and prenatal testing or preimplantation genetic diagnosis for pregnancies can be options considered for genetic counseling.
Dopamine transporter deficiency syndrome
Gerstmann syndrome
Scheie syndrome
Dopamine beta hydroxylase deficiency
Ohtahara syndrome
Pallister–Killian syndrome
Dopamine dysregulation syndrome
Gerstmann–Sträussler–Scheinker syndrome