Homo sapiens Genome sequencing. Homo sapiens

In the present study, a 3.5-year-old female in a consanguineous Iranian family with an initial diagnostic of gait imbalance and speech delay has been identified. Doing some investigations such as neuroimaging, because of the heterogeneity of neurogenetic disorders, we utilized whole-exome sequencing (WES) to identify the possible genetic defects. WES identified a novel homozygous in-frame indel variant, c.1139_1150del; p.(Gly380_Lys384delinsGlu), in SLC6A3 gene (NM_001044.4), as the most likely disease-susceptibility variant confirmed by Sanger sequencing. 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. Also, we showed that the identified variant in EL4 region leads to DTDS in this case. However, it needs to be confirmed by other complementary studies especially via using animal models.