{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:19:08Z","timestamp":1790194748619,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T00:00:00Z","timestamp":1632096000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>SHQ1 is essential for biogenesis of H\/ACA ribonucleoproteins, a class of molecules important for processing ribosomal RNAs, modifying spliceosomal small nuclear RNAs and stabilizing telomerase. Components of the H\/ACA ribonucleoprotein complex have been linked to neurological developmental defects. Here, we report two sibling pairs from unrelated families with compound heterozygous variants in SHQ1. Exome sequencing was used to detect disease causing variants, which were submitted to \u2018matching\u2019 platforms linked to MatchMaker Exchange. Phenotype comparisons supported these matches. The affected individuals present with early-onset dystonia, with individuals from one family displaying additional neurological phenotypes, including neurodegeneration. As a result of cerebrospinal fluid studies suggesting possible abnormal dopamine metabolism, a trial of levodopa replacement therapy was started but no clear response was noted. We show that fibroblasts from affected individuals have dramatic loss of SHQ1 protein. Variants from both families were expressed in Saccharomyces cerevisiae, resulting in a strong reduction in H\/ACA snoRNA production and remarkable defects in rRNA processing and ribosome formation. Our study identifies SHQ1 as associated with neurological disease, including early-onset dystonia, and begins to delineate the molecular etiology of this novel condition.<\/jats:p>","DOI":"10.1093\/hmg\/ddab247","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T19:20:09Z","timestamp":1631733609000},"page":"614-624","source":"Crossref","is-referenced-by-count":23,"title":["Compound heterozygous variants in <i>SHQ1<\/i> are associated with a spectrum of neurological features, including early-onset dystonia"],"prefix":"10.1093","volume":"31","author":[{"given":"Sophie","family":"Sleiman","sequence":"first","affiliation":[{"name":"Centre d\u2019excellence en recherche sur les maladies orphelines \u2013 Fondation Courtois (CERMO-FC), D\u00e9partement des sciences biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, H3C 3P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aren E","family":"Marshall","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Dong","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziz","family":"Mhanni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E0W2, Canada"},{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isma\u00ebl","family":"Alidou-D\u2019Anjou","sequence":"additional","affiliation":[{"name":"Centre d\u2019excellence en recherche sur les maladies orphelines \u2013 Fondation Courtois (CERMO-FC), D\u00e9partement des sciences biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, H3C 3P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Frosk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E0W2, Canada"},{"name":"Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha E","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zornitza","family":"Stark","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc R","family":"Del Bigio","sequence":"additional","affiliation":[{"name":"Department of Pathology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, R3E0W2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arran","family":"McBride","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Sadedin","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndon","family":"Gallacher","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Care4Rare Canada Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Melbourne, VIC 3052, Australia"},{"name":"Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kym M","family":"Boycott","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Dragon","sequence":"additional","affiliation":[{"name":"Centre d\u2019excellence en recherche sur les maladies orphelines \u2013 Fondation Courtois (CERMO-FC), D\u00e9partement des sciences biologiques, Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, H3C 3P8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin D","family":"Kernohan","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, Ottawa, K1H 8L1, Canada"},{"name":"Newborn Screening Ontario, Children's Hospital of Eastern Ontario, Ottawa ON, K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,20]]},"reference":[{"key":"2022022310593596700_ref1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.trsl.2014.04.003","article-title":"RNA epigenetics","volume":"165","author":"Liu","year":"2015","journal-title":"Transl. 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Acids Res."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab247\/40511370\/ddab247.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/4\/614\/42579490\/ddab247.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/4\/614\/42579490\/ddab247.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T12:52:08Z","timestamp":1645620728000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/31\/4\/614\/6372548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,20]]},"references-count":34,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,9,20]]},"published-print":{"date-parts":[[2022,2,21]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab247","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,2,15]]},"published":{"date-parts":[[2021,9,20]]}}}