{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:26:54Z","timestamp":1790105214594,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2016,5,2]],"date-time":"2016-05-02T00:00:00Z","timestamp":1462147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000233","name":"Genome British Columbia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>In 1987 Fitzsimmons and Guilbert described identical male twins with progressive spastic paraplegia, brachydactyly with cone shaped epiphyses, short stature, dysarthria, and \u201clow\u2010normal\u201d intelligence. In subsequent years, four other patients, including one set of female identical twins, a single female child, and a single male individual were described with the same features, and the eponym Fitzsimmons syndrome was adopted (OMIM #270710). We performed exome analysis of the patient described in 2009, and one of the original twins from 1987, the only patients available from the literature. No single genetic etiology exists that explains Fitzsimmons syndrome; however, multiple different genetic causes were identified. Specifically, the twins described by Fitzsimmons had heterozygous mutations in the <jats:italic>SACS<\/jats:italic> gene, the gene responsible for autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS), as well as a heterozygous mutation in the <jats:italic>TRPS1<\/jats:italic>, the gene responsible in Trichorhinophalangeal syndrome type 1 (TRPS1 type 1) which includes brachydactyly as a feature. A <jats:italic>TBL1XR1<\/jats:italic> mutation was identified in the patient described in 2009 as contributing to his cognitive impairment and autistic features with no genetic cause identified for his spasticity or brachydactyly. The findings show that these individuals have multiple different etiologies giving rise to a similar phenotype, and that \u201cFitzsimmons syndrome\u201d is in fact not one single syndrome. Over time, we anticipate that continued careful phenotyping with concomitant genome\u2010wide analysis will continue to identify the causes of many rare syndromes, but it will also highlight that previously delineated clinical entities are, in fact, not syndromes at all. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37684","type":"journal-article","created":{"date-parts":[[2016,5,2]],"date-time":"2016-05-02T06:07:18Z","timestamp":1462169238000},"page":"1820-1825","source":"Crossref","is-referenced-by-count":23,"title":["Syndrome disintegration: Exome sequencing reveals that Fitzsimmons syndrome is a co\u2010occurrence of multiple events"],"prefix":"10.1002","volume":"170","author":[{"given":"Christine M.","family":"Armour","sequence":"first","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taila","family":"Hartley","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi Warman","family":"Chardon","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sawyer","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Schwartzentruber","sequence":"additional","affiliation":[{"name":"McGill University and Genome Quebec Innovation Centre Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Hennekam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Academic Medical Centre, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Majewski","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis E.","family":"Bulman","sequence":"additional","affiliation":[{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"FORGE Canada Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohnish","family":"Suri","sequence":"additional","affiliation":[{"name":"Nottingham Clinical Genetics Service City Hospital Campus, Nottingham University Hospitals NHS Trust Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kym M.","family":"Boycott","sequence":"additional","affiliation":[{"name":"Department of Genetics Children's Hospital of Eastern Ontario Ottawa Canada"},{"name":"Children's Hospital of Eastern Ontario Research Institute University of Ottawa Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1866-1955-6-17"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.05.003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3555"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16011312"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.001"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.24.11.702"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102015\u2010103233"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.3.251"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990521)84:2<90::AID-AJMG2>3.0.CO;2-8"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2015.03.002"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227764"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10989"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36759"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2014.71"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12654"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36619"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000331319"},{"key":"e_1_2_6_20_1","volume-title":"GeneReviews(R)","author":"Vermeer S","year":"2003"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07999"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306555"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.14601"}],"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.37684","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37684","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T23:19:34Z","timestamp":1696547974000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,2]]},"references-count":22,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1002\/ajmg.a.37684"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37684","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,2]]}}}