{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T22:54:16Z","timestamp":1774047256000,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Spinal muscular atrophy with congenital bone fractures 2 is a rare and severe autosomal recessive neuromuscular disorder caused by pathogenic variants in\n                    <jats:italic>ASCC1<\/jats:italic>\n                    . This condition characterized by prenatal onset of severe hypotonia with fetal hypokinesia and congenital contractures results in arthrogryposis multiplex congenita, and increased incidence of prenatal fractures. To date, only truncating variants, loss of function and splicing variants have been described. Here, we report the first homozygous missense variant in\n                    <jats:italic>ASCC1<\/jats:italic>\n                    identified prenatally in two full siblings with fetal akinesia deformation sequence. This variant affects a highly conserved residue within the RNA\u2010ligase\u2010like domain and leads to a nearly total absence of ASCC1 protein in muscle. This report broadens the knowledge on the pathogenesis of this disorder showing that missense variants should also be considered. It also highlights the importance of precise ultrasound examination combined with molecular genetic testing in the prenatal diagnosis of this severe neuromuscular disorder.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64301","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:46:40Z","timestamp":1763027200000},"page":"744-748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variant Update on\n                    <scp>\n                      <i>ASCC1<\/i>\n                    <\/scp>\n                    : Characterization of the First Homozygous Missense Variant Involved in Prenatal\u2010Onset Spinal Muscular Atrophy With Congenital Bone Fractures 2"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9094-6612","authenticated-orcid":false,"given":"A.","family":"Civit","sequence":"first","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Kerbellec","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Laurenceau","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. C.","family":"Ung","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours, INSERM, Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. P.","family":"Moizard","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Ronce","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Gueguen","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM, Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Laumonnier","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM, Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. C.","family":"Br\u00e9hin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Pathological Cytology, Department of Genetics and Reference Center for Developmental Abnormalities Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Marguet","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Pathological Cytology, Department of Genetics and Reference Center for Developmental Abnormalities Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Laquerri\u00e8re","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM U1245, Team Epigenetics and Pathophysiology of Neurodevelopmental Disorders and Department of Pathology Rouen University Hospital  Rouen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. M.","family":"Bergemer Fouquet","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Pathological Cytology Tours University Hospital, University of Tours  France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Cirier","sequence":"additional","affiliation":[{"name":"Department of Gynecology Bourges Hospital  Bourges France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Blesson","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Arpin","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM, Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Jeanne","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM, Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1080-972X","authenticated-orcid":false,"given":"M. L.","family":"Vuillaume","sequence":"additional","affiliation":[{"name":"Genetics Department Tours University Hospital  Tours France"},{"name":"Universit\u00e9 de Tours, INSERM, Imaging Brain &amp; Neuropsychiatry iBraiN U1253  Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet\u20102018\u2010105390"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14130"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006045\u20100"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg7492"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.6519"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61431"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.01.006"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1222"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1212"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104537"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116039"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2021.100024"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.176601"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12997"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62219"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.111"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62898"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1137573"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.64301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T21:14:38Z","timestamp":1771103678000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,13]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/ajmg.a.64301"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64301","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,13]]},"assertion":[{"value":"2025-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}