{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:53:06Z","timestamp":1789545186298,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T00:00:00Z","timestamp":1537660800000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p><jats:italic>PNPT1<\/jats:italic> is a mitochondrial RNA transport protein that has been linked to two discrete phenotypes, namely isolated sensorineural hearing loss (OMIM 614934) and combined oxidative phosphorylation deficiency (OMIM 614932). The latter has been described in multiple families presenting with complex neurologic manifestations in childhood. We describe adult siblings with biallelic <jats:italic>PNPT1<\/jats:italic> variants identified through WES who presented with isolated severe congenital sensorineural hearing loss (SNHL). In their 40s, they each developed and then followed a nearly identical neurodegenerative course with ataxia, dystonia, and cognitive decline. Now in their 50s and 60s, all have developed the additional features of optic nerve atrophy, spasticity, and incontinence. The natural history of the condition in this family may suggest that the individuals previously reported as having isolated SNHL may be at risk of developing multisystem disease in late adulthood, and that <jats:italic>PNPT1<\/jats:italic>\u2010related disorders may constitute a spectrum rather than distinct phenotypes.<\/jats:p>","DOI":"10.1002\/ajmg.a.40516","type":"journal-article","created":{"date-parts":[[2018,9,23]],"date-time":"2018-09-23T14:49:52Z","timestamp":1537714192000},"page":"2487-2493","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Is <i>PNPT1<\/i>\u2010related hearing loss ever non\u2010syndromic? Whole exome sequencing of adult siblings expands the natural history of <i>PNPT1<\/i>\u2010related disorders"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0512-0429","authenticated-orcid":false,"given":"Alison","family":"Eaton","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois P.","family":"Bernier","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Goedhart","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Caluseriu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University of Alberta  Edmonton Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7720-068X","authenticated-orcid":false,"given":"Ryan E.","family":"Lamont","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kym M.","family":"Boycott","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa  Ottawa Ontario"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian S.","family":"Parboosingh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-5467","authenticated-orcid":false,"given":"A. Micheil","family":"Innes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Alberta Children's Hospital Research Institute, Cumming School of Medicine University of Calgary  Calgary Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Care4Rare Canada Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2016.128"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.05.003"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2007.09.006"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2011.08.019"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13101"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.otc.2015.07.007"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx221"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.177"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1808-8694(15)31313-6"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-016-0930-9"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13068"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12543"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.09.001"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.09.002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.035"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-015-9823-y"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.40516","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.40516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:15:19Z","timestamp":1694697319000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.40516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,23]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/ajmg.a.40516"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.40516","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,23]]},"assertion":[{"value":"2018-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}