Homozygous in-frame variant of SCL6A3 causes dopamine transporter deficiency syndrome in a consanguineous family
| Autor: | Sareh Hosseinpour, Ali Reza Tavasoli, Masoud Garshasbi, Ehsan Razmara, Erfan Heidari |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Synaptic cleft Dopamine transport Iran Protein Structure Secondary 03 medical and health sciences Consanguinity Dopamine Genetics medicine Extracellular Humans Gene Genetics (clinical) 030304 developmental biology Dopamine transporter Family Health 0303 health sciences Dopamine Plasma Membrane Transport Proteins Dopamine transporter deficiency syndrome biology 030305 genetics & heredity Homozygote Parkinson Disease Pedigree Dystonic Disorders Child Preschool Mutation biology.protein Female Homeostasis medicine.drug |
| Zdroj: | Annals of human geneticsREFERENCES. 84(4) |
| ISSN: | 1469-1809 |
| Popis: | The human dopamine transporter (hDAT) participates in dopamine homeostasis by clearing dopamine from the extracellular space using secondary active transport. Dysregulation of hDAT has been reported to be associated with different neuropsychiatric disorders. Dopamine transporter deficiency syndrome (DTDS) is a complex disease caused by defects in dopamine uptake within the synaptic cleft and patients manifest parkinsonian features. The extracellular loops are crucial for DAT activity and defects in these regions disturb dopamine transport. In the present study, a 3.5-year-old female in a consanguineous Iranian family with an initial diagnosis of gait imbalance and speech delay has been identified. We utilized whole-exome sequencing (WES) to identify the possible genetic defect(s). WES identified a novel homozygous in-frame indel variant, c.1139_1150del; p.(Gly380_Lys384delinsGlu), in the SLC6A3 gene (NM_001044.4), as the most likely disease-susceptibility variant. This variant is located in extracellular loop 4 (EL4) of the DAT protein. Our study highlights the role of extracellular loops and shows the EL4 of hDAT as a critical region for the protein activity. The identified variant in the EL4 region of DAT is predicted to compromise DAT function and may lead to DTDS in this case. However, complementary studies are required to confirm. |
| Databáze: | OpenAIRE |
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