New Term Request: Parkinsonism-dystonia, infantile 1 -OR- dopamine transporter deficiency syndrome (name TBD)

[vjenkinsFB]

I'd like to request a term for Parkinsonism-dystonia, infantile 1 -or- dopamine transporter deficiency syndrome. Authors vary in the names, see references below, I’ll let you make that call. Some sites have one entry for each.

OMIM: https://omim.org/entry/613135

Potential definition: [[NAME]] has_material_basis_in the SLC6A3 gene on chromosome 5p15.

Potential parent term: Parkinson’s disease

Synonyms: PKDYS1, dopamine transporter deficiency syndrome, DTDS, DAT deficiency, infantile parkinsonism-dystonia

ClinVar search term: SLC6A3[gene] AND ((1[VARLEN] : 1000[VARLEN] AND "single gene"[Properties]))

MedGen page(s) pointed to by the above: Most point to Parkinsonism-dystonia, infantile (https://www.ncbi.nlm.nih.gov/medgen/C2751067/). Some point to Classic dopamine transporter deficiency syndrome (https://www.ncbi.nlm.nih.gov/medgen/CN035598/) which has Parkinsonism-dystonia infantile as a synonym. See Ng et al for more on this.

If you go with DTDS, Nahesi et al delineates classic vs atypical DTDS. OTOH, Aguilar et al claim DTDS is a distinct type of infantile parkinsonism-dystonia.

GeneReviews page: https://www.ncbi.nlm.nih.gov/books/NBK442323/

Medline: https://medlineplus.gov/genetics/condition/dopamine-transporter-deficiency-syndrome/

RareDiseases: https://rarediseases.org/gard-rare-disease/dopamine-transporter-deficiency-syndrome/

MalaCards page: unhelpfully has both https://www.malacards.org/card/parkinsonism_dystonia_1_infantile_onset and https://www.malacards.org/card/slc6a3_related_dopamine_transporter_deficiency_syndrome

HGNC entry for gene: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/11049

Citations other than those in the OMIM entry:

• https://pubmed.ncbi.nlm.nih.gov/24613933/ Ng J, Zhen J, Meyer E, et al. Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood. Brain. 2014;137(Pt 4):1107-1119. doi:10.1093/brain/awu022
• https://pubmed.ncbi.nlm.nih.gov/34002696/ Aguilar JI, Cheng MH, Font J, et al. Psychomotor impairments and therapeutic implications revealed by a mutation associated with infantile Parkinsonism-Dystonia. Elife. 2021;10:e68039. Published 2021 May 18. doi:10.7554/eLife.68039
• https://pubmed.ncbi.nlm.nih.gov/34011628/ Ng J, Barral S, De La Fuente Barrigon C, et al. Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism. Sci Transl Med. 2021;13(594):eaaw1564. doi:10.1126/scitranslmed.aaw1564
• https://pubmed.ncbi.nlm.nih.gov/27353511/ Lu Q, Song Z, Deng X, et al. SLC6A3 rs28363170 and rs3836790 variants in Han Chinese patients with sporadic Parkinson's disease. Neurosci Lett. 2016;629:48-51. doi:10.1016/j.neulet.2016.06.053
• https://pubmed.ncbi.nlm.nih.gov/25212851/ Habak C, Noreau A, Nagano-Saito A, et al. Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease. Brain. 2014;137(Pt 11):3025-3035. doi:10.1093/brain/awu251
• https://pubmed.ncbi.nlm.nih.gov/32646530/ Baga M, Spagnoli C, Soliani L, et al. Early-onset Dopamine Transporter Deficiency Syndrome: Long-term Follow-up. Can J Neurol Sci. 2021;48(2):285-286. doi:10.1017/cjn.2020.144
• https://pubmed.ncbi.nlm.nih.gov/32077500/ Heidari E, Razmara E, Hosseinpour S, Tavasoli AR, Garshasbi M. Homozygous in-frame variant of SCL6A3 causes dopamine transporter deficiency syndrome in a consanguineous family. Ann Hum Genet. 2020;84(4):315-323. doi:10.1111/ahg.12378
• https://pubmed.ncbi.nlm.nih.gov/27519790/ Illiano P, Lanzo A, Leo D, et al. A Caenorhabditis elegans model to study dopamine transporter deficiency syndrome. Eur J Neurosci. 2017;45(1):207-214. doi:10.1111/ejn.13366
• https://pubmed.ncbi.nlm.nih.gov/33015223/ Nasehi MM, Nikkhah A, Salari M, Soltani P, Shirzadi S. Dopamine Transporter Deficiency Syndrome: A Case with Hyper- and Hypokinetic Extremes. Mov Disord Clin Pract. 2020;7(Suppl 3):S57-S60. Published 2020 Sep 29. doi:10.1002/mdc3.13064
• https://pubmed.ncbi.nlm.nih.gov/28972153/ Asjad HMM, Kasture A, El-Kasaby A, et al. Pharmacochaperoning in a Drosophila model system rescues human dopamine transporter variants associated with infantile/juvenile parkinsonism. J Biol Chem. 2017;292(47):19250-19265. doi:10.1074/jbc.M117.797092

FlyBase paper(s) to curate with this term: FBrf0249040, FBrf0251408, FBrf0237249.

My contact info: vjenkins@morgan.harvard.edu (FlyBase), 0000-0002-1567-7626. Thank you!

[csbjohnson]

Thank you very much for your Parkinsonism-dystonia, infantile 1 -or- dopamine transporter deficiency syndrome term request @vjenkinsFB. We'll review it, get back to you soon and update the DO for the next release.

Thank you!

[vjenkinsFB]

@csbjohnson , @lschriml , I'm just cleaning out my back catalog of DO terms to request (2/3 done), which is why there are so many from me today. I'm not expecting them to be done ASAP, or in order; just wanted to get the process started. Thanks!

[csbjohnson]

Great, thank you for the requests and for letting us know! @vjenkinsFB

[allenbaron]

The clinical literature almost invariably calls this SLC6A3 gene-related disease 'dopamine transporter deficiency syndrome' (DTDS), and has clearly delineated 'classic' and 'atypical' forms, which differ in offset and somewhat in phenotype. All three of these will be included in the next release with 'classic dopamine transporter deficiency syndrome' (DOID:0070489) corresponding to the original requested disease (OMIM:613135).

'atypical dopamine transporter deficiency syndrome' has been described as caused by heterozygous (dominant negative) variants and homozygous/compound heterozygous (partial loss of function) variants and is not yet captured by an entry in the clinical vocabularies considered authoritative (OMIM, Orphanet), meaning this disease currently lacks cross-references.

[vjenkinsFB]

I'll take it! Thank you @allenbaron !