@article{1d53fccd863d4825a0855b69af0e597b,
title = "Novel THAP1 missense variant with incomplete penetrance in a case of generalized young onset dystonia showing good response to deep brain stimulation",
abstract = "We describe a case of young onset generalized dystonia, harboring a previously unreported likely pathogenic THAP1 missense variant (c.109 G > A; p.Glu37Lys) that was inherited from her unaffected father. Moreover, we report a positive effect of deep brain stimulation, particularly on the cervical component of dystonia.",
keywords = "Deep brain stimulation, Generalized dystonia, Incomplete penetrance, Pathogenic variant, THAP1",
author = "{Keller Sarmiento}, {Ignacio J.} and Avram Fraint and Lisa Kinsley and Akhtar, {Rizwan S.} and Vincenzo Silani and Lubbe, {Steven J.} and Dimitri Krainc and Mencacci, {Niccol{\`o} E.}",
note = "Funding Information: N.E.M. is funded by a Parkinson's Foundation grant. Funding Information: I.J.K.S. is supported by the Align Sience Across Parkinson's (ASAP) Global Parkinson's Genetics Program (GP2). Funding Information: To investigate a possible genetic etiology, an extensive panel for dystonia was ordered, which identified a previously unreported variant in THAP1 (NM_018105.2; exon 2 c.109 G > A; p.Glu37Lys), inherited from her unaffected father. Only one carrier (1/125,682) is reported in the genome aggregation database (gnomAD v2.1.1; https://gnomad.broadinstitute.org/). Whole-exome sequencing was additionally performed as reported elsewhere [3]. This analysis excluded additional relevant pathogenic variants in an extended list of genes linked to movement disorders or other de novo or bi-allelic variants in novel candidate disease-associated genes (Supplemental Table 1). According to ACMG/AMP guidelines, this variant is classified as likely pathogenic, meeting 2 moderate evidence (PM1, PM2) and 2 supporting evidence criteria (PP3, PP4) [4].V.S. received compensation for consulting services and/or speaking activities from AveXis, Cytokinetics, Italfarmaco, Liquidweb S.r.l., Novartis Pharma AG and Zambon. Receives or has received research supports form the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. He is in the Editorial Board of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, European Neurology, American Journal of Neurodegenerative Diseases, Frontiers in Neurology.N.E.M. is funded by a Parkinson's Foundation grant. Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",
year = "2022",
month = dec,
doi = "10.1016/j.parkreldis.2022.10.022",
language = "English (US)",
volume = "105",
pages = "7--8",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",
}