{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:48:49Z","timestamp":1771274929961,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010year\u2010old female in a consanguineous Iranian family with an initial diagnosis of gait imbalance and speech delay has been identified. We utilized whole\u2010exome sequencing (WES) to identify the possible genetic defect(s). WES identified a novel homozygous in\u2010frame indel variant, c.1139_1150del; p.(Gly380_Lys384delinsGlu), in the <jats:italic>SLC6A3<\/jats:italic> gene (NM_001044.4), as the most likely disease\u2010susceptibility 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.<\/jats:p>","DOI":"10.1111\/ahg.12378","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T10:41:31Z","timestamp":1582195291000},"page":"315-323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Homozygous in\u2010frame variant of <i>SCL6A3<\/i> causes dopamine transporter deficiency syndrome in a consanguineous family"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8361-4096","authenticated-orcid":false,"given":"Erfan","family":"Heidari","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-3975","authenticated-orcid":false,"given":"Ehsan","family":"Razmara","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sareh","family":"Hosseinpour","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic Pediatric Neurology Division Children's Medical Center Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-5809","authenticated-orcid":false,"given":"Ali Reza","family":"Tavasoli","sequence":"additional","affiliation":[{"name":"Myelin Disorders Clinic Pediatric Neurology Division Children's Medical Center Pediatrics Center of Excellence Tehran University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-7903","authenticated-orcid":false,"given":"Masoud","family":"Garshasbi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medical Sciences Tarbiat Modares University  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,2,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000126440.16612.51"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(01)00122-5"},{"issue":"6","key":"e_1_2_10_4_1","first-page":"1455","article-title":"Infantile parkinsonism\u2010dystonia: A dopamine \u201ctransportopathy.\u201d","volume":"119","author":"Blackstone C.","year":"2009","journal-title":"The Journal of Clinical Investigation"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2009.00760.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)02044-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(93)90029-J"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00235"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2019.00080"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(97)00131-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.108.000869"},{"issue":"6","key":"e_1_2_10_12_1","first-page":"1595","article-title":"Homozygous loss\u2010of\u2010function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism\u2010dystonia","volume":"119","author":"Kurian M. 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