{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:14:15Z","timestamp":1790522055475,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T00:00:00Z","timestamp":1582156800000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Arthrogryposis multiplex congenita (AMC) is defined as congenital, non\u2010progressive contractures in more than two joints and in multiple body areas, resulting from reduced fetal mobility. So far, more than 400 causative genes for AMC have been identified. Some isolated AMC phenotypes arise as a result of mutations in genes encoding components required for motor neuron structure, function, and myelination, as in the case of\n                    <jats:italic>ADCY6<\/jats:italic>\n                    encoding the enzyme adenylyl cyclase type 6. ADCY6 inactivation, due to biallelic variants, have been previously associated with the lethal congenital contracture syndrome 8 (LCCS8). So far, only four LCCS8 patients, from two families, have been reported. Here, we describe a new patient affected by a severe form of AMC, harboring two novel compound heterozygous variants in\n                    <jats:italic>ADCY6<\/jats:italic>\n                    . Our findings expand the clinical and mutational spectrum of LCCS8, showing a possible correlation between the impact of the ADCY6 missense variants reported to date, predicted by molecular modeling, and the severity of the phenotype.\n                  <\/jats:p>","DOI":"10.1111\/cge.13691","type":"journal-article","created":{"date-parts":[[2019,12,17]],"date-time":"2019-12-17T10:11:37Z","timestamp":1576577497000},"page":"649-654","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Expanding the clinical and molecular spectrum of lethal congenital contracture syndrome 8 associated with biallelic variants\n                    <i>of ADCY6<\/i>"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics Unit Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1628-5488","authenticated-orcid":false,"given":"Claudio","family":"Cherchi","sequence":"additional","affiliation":[{"name":"Respiratory Unit, Academic Department of Pediatrics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Genetics and Rare Diseases Research Division Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Department of Pediatric Specialties Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Cocciadiferro","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Unit Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Cutrera","sequence":"additional","affiliation":[{"name":"Respiratory Unit, Academic Department of Pediatrics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria B.","family":"Chiarini Testa","sequence":"additional","affiliation":[{"name":"Respiratory Unit, Academic Department of Pediatrics Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Barone","sequence":"additional","affiliation":[{"name":"Medical Genetics, Referral Centre for Rare Genetic Diseases, ARNAS Garibaldi  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Bianca","sequence":"additional","affiliation":[{"name":"Medical Genetics, Referral Centre for Rare Genetic Diseases, ARNAS Garibaldi  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics Unit Ospedale Pediatrico Bambino Ges\u00f9  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2016.57578"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.03.008"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt618"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.07.023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00303253"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/374421a0"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20819"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2016.09.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.014"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23297"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320440110"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0014-2956.2001.02708.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607522200"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12913"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13691","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13691","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13691","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13691","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T03:14:23Z","timestamp":1694056463000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,20]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4]]}},"alternative-id":["10.1111\/cge.13691"],"URL":"https:\/\/doi.org\/10.1111\/cge.13691","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13691\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13691\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13691\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13691\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13691\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,20]]},"assertion":[{"value":"2019-11-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}