X-linked dystonia-parkinsonism (XDP) associated with antisense insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon within an intron of TAF1. Clinical features include focal and generalised dystonia, parkinsonism, cognitive dysfunction. XX individuals who are heterozygous carriers usually do not develop the full syndrome, although some patients have non-progressive focal dystonia with parkinsonism. Disease severity is associated with number of hexanucleotide repeats within the SVA. (Adapted)¹.

Prevalence

Philippines overall 0.34:100,000. Panay Islands 5.24:100,000. Capiz province 18.9:100,000. To date, all known cases to date are of Filipino descent¹.

Age of Onset

Average age of onset for XDP is 39.7 years in males, 52 years in females, range 12-79 years. ~99% of cases are male^2,1,3.

HPO Terms

–

Association

Mendelian

Locus

hg19 chrX:70672904-70672981

hg38 chrX:71453054-71453131

t2t chrX:69887153-69887230

Details

Strong inverse relationship between age of onset and insertion length, which varied between 35-52 repeats².

Mechanism

LoF

Altered splicing with intron retention, haploinsufficiency¹.

Detection

Year

2017²

Location in Gene

Intron 32

Gene Strand

Alleles

Ref. Motif

AGAGGG

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

AGAGGG

Pathogenic (gene)

AGAGGG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interruption (gene)

–

References

Direct supporting references for info on this page.

Neurological disorders caused by novel non-coding repeat expansions: clinical features and differential diagnosis.

Elisa,Vegezzi, Hiroyuki,Ishiura, D Cristopher,Bragg, David,Pellerin, Francesca,Magrinelli, Riccardo,Currò, Stefano,Facchini, Arianna,Tucci, John,Hardy, Nutan,Sharma, Matt C,Danzi, Stephan,Zuchner, Bernard,Brais, Mary M,Reilly, Shoji,Tsuji, Henry,Houlden, Andrea,Cortese

The Lancet. Neurology · 2024-07-01

pmid:38876750

Disease onset in X-linked dystonia-parkinsonism correlates with expansion of a hexameric repeat within an SVA retrotransposon in

D Cristopher,Bragg, Kotchaphorn,Mangkalaphiban, Christine A,Vaine, Nichita J,Kulkarni, David,Shin, Rachita,Yadav, Jyotsna,Dhakal, Mai-Linh,Ton, Anne,Cheng, Christopher T,Russo, Mark,Ang, Patrick,Acuña, Criscely,Go, Taylor N,Franceour, Trisha,Multhaupt-Buell, Naoto,Ito, Ulrich,Müller, William T,Hendriks, Xandra O,Breakefield, Nutan,Sharma, Laurie J,Ozelius

Proceedings of the National Academy of Sciences of the United States of America · 2017-12-11

pmid:29229810

Phenotypic and molecular analyses of X-linked dystonia-parkinsonism ("lubag") in women.

Virgilio Gerald H,Evidente, Dagmar,Nolte, Stephan,Niemann, Joel,Advincula, Mezzanie C,Mayo, Filipinas F,Natividad, Ulrich,Müller

Archives of neurology · 2004-12-01

pmid:15596620

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

MSH3 is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism.

Alan,Mejia Maza, Madison,Hincher, Kevin,Correia, Tammy,Gillis, Ayumi,Nishiyama, Ellen B,Penney, Aloysius,Domingo, Rachita,Yadav, Micaela G,Murcar, Patrick D,Villafria Mercado, Justin S,Han, Ean P,Norenberg, Cara,Fernandez-Cerado, G Paul,Legarda, Michelle,Sy, Edwin L,Muñoz, Mark C,Ang, Cid Czarina E,Diesta, Criscely,Go, Nutan,Sharma, D Cristopher,Bragg, Michael E,Talkowski, Marcy E,MacDonald, Jong-Min,Lee, Laurie J,Ozelius, Vanessa Chantal,Wheeler

American journal of human genetics · 2025-12-23

pmid:41443196

Alan Mejia,Maza, Madison,Hincher, Kevin,Correia, Tammy,Gillis, Ayumi,Nishiyama, Ellen B,Penney, Aloysius,Domingo, Rachita,Yadav, Micaela G,Murcar, Patrick D Villafria,Mercado, Justin S,Han, Ean P,Norenberg, Cara,Fernandez-Cerado, G Paul,Legarda, Michelle,Sy, Edwin,Muñoz, Mark C,Ang, Cid Czarina E,Diesta, Criscely,Go, Nutan,Sharma, D Cristopher,Bragg, Michael E,Talkowski, Marcy E,MacDonald, Jong-Min,Lee, Laurie J,Ozelius, Vanessa Chantal,Wheeler

bioRxiv : the preprint server for biology · 2025-05-16

pmid:40463055

Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease.

Vivien,Horváth, Raquel,Garza, Marie E,Jönsson, Pia A,Johansson, Anita,Adami, Georgia,Christoforidou, Ofelia,Karlsson, Laura,Castilla Vallmanya, Symela,Koutounidou, Patricia,Gerdes, Ninoslav,Pandiloski, Christopher H,Douse, Johan,Jakobsson

Nature structural & molecular biology · 2024-06-04

pmid:38834915

Stability of Mosaic Divergent Repeat Interruptions in X-Linked Dystonia-Parkinsonism.

Joshua,Laß, Theresa,Lüth, Kathleen,Schlüter, Susen,Schaake, Björn-Hergen,Laabs, Christoph,Much, Roland Dominic,Jamora, Raymond L,Rosales, Gerard,Saranza, Cid Czarina E,Diesta, Christopher E,Pearson, Inke R,König, Norbert,Brüggemann, Christine,Klein, Ana,Westenberger, Joanne,Trinh

Movement disorders : official journal of the Movement Disorder Society · 2024-04-14

pmid:38616406

The Effect of Glucocorticoids on

Sam Ezrael Dela,Cruz, Pia,Bagamasbad

Journal of the ASEAN Federation of Endocrine Societies · 2022-08-07

pmid:37234925

Repeat-Associated Non-AUG Translation of AGAGGG Repeats that Cause X-Linked Dystonia-Parkinsonism.

Charles Jourdan,Reyes, Katsura,Asano, Peter K,Todd, Christine,Klein, Aleksandar,Rakovic

Movement disorders : official journal of the Movement Disorder Society · 2022-08-16

pmid:35971992

Factors influencing reduced penetrance and variable expressivity in X-linked dystonia-parkinsonism.

Jelena,Pozojevic, Björn-Hergen,von Holt, Ana,Westenberger

Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2022-08-12

pmid:38835911

Variation in TAF1 Expression in Female Carrier-Induced Pluripotent Stem Cells and Human Brain Ontogeny Has Implications for Adult Neostriatum Vulnerability in X-Linked Dystonia Parkinsonism.

Laura,D'Ignazio, Ricardo S,Jacomini, Bareera,Qamar, Kynon J M,Benjamin, Ria,Arora, Tomoyo,Sawada, Taylor A,Evans, Kenneth E,Diffenderfer, Aimee R,Pankonin, William T,Hendriks, Thomas M,Hyde, Joel E,Kleinman, Daniel R,Weinberger, D Cristopher,Bragg, Apua C M,Paquola, Jennifer A,Erwin

eNeuro · 2022-08-30

pmid:35868859

Mosaic divergent repeat interruptions in XDP influence repeat stability and disease onset.

Joanne,Trinh, Theresa,Lüth, Susen,Schaake, Björn-Hergen,Laabs, Kathleen,Schlüter, Joshua,Laβ, Jelena,Pozojevic, Ronnie,Tse, Inke,König, Roland Dominic,Jamora, Raymond L,Rosales, Norbert,Brüggemann, Gerard,Saranza, Cid Czarina E,Diesta, Frank J,Kaiser, Christel,Depienne, Christopher E,Pearson, Ana,Westenberger, Christine,Klein

Brain : a journal of neurology · 2023-03-01

pmid:35481544

Locus XDP TAF1

Disease

Locus

Alleles

References

Additional Literature