{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:16:09Z","timestamp":1790615769258,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We present a patient with congenital myopathy and an inborn epiphysiolysis of the ulna. Whole\u2010exome sequencing analysis revealed two novel mutations in Activation Signal Cointegrator Complex 1 (<jats:italic>ASCC1<\/jats:italic>) gene in a compound heterozygous state\u2014a splicing variant c.395\u20102A&gt;G and a deletion of the first two coding exons. Homozygous and compound heterozygous LoF variants in <jats:italic>ASCC1<\/jats:italic> gene lead to a severe phenotype of spinal muscular atrophy with congenital bone fractures 2 (SMABF2). All patients described to date presented with a severe muscular hypotony, inborn fractures, and passed away shortly after birth while our proband had moderate hypotony, no fractures, but epiphysiolysis and he was 3.5\u2009years old at the time of examination. To explain the phenotype of our patient, we performed an RNA analysis of all family members. We discovered that the c.395\u20102A&gt;G variant results in two aberrant mRNA isoforms. We also validated the deletion of two exons in <jats:italic>ASCC1<\/jats:italic> gene that lead to the increased expression of this truncated transcript by 1.8 times. To investigate the possible impact of this deletion on the phenotype we predicted a new Kozak sequence in exon 4 that could lead to the formation of a truncated protein with shortened KH domain and a full RNA ligase\u2010like domain. We suggest that this unexpectedly different phenotype of the proband with <jats:italic>ASCC1<\/jats:italic>\u2010related disorder could be explained by the presence of the truncated protein with an increased expression.<\/jats:p>","DOI":"10.1002\/ajmg.a.62898","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T10:28:36Z","timestamp":1657880916000},"page":"3100-3105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Congenital myopathy as a new phenotype caused by two undescribed variants in <scp><i>ASCC1<\/i><\/scp> gene"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-6915","authenticated-orcid":false,"given":"Margarita","family":"Sharova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Guseva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Kurenkov","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Children's Health, the Russian Federation Ministry of Healthcare  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Novoselova","sequence":"additional","affiliation":[{"name":"Genomed Ltd., Genetic Diagnostic Lab  Moscow Russia"},{"name":"Filatov N.F. Children's City Hospital 103001  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysylu","family":"Murtazina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105390"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab357"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bti767"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.22.14.5203-5211.2002"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.01.006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1708-9"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0209185"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116039"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00109"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/16.11.960"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12997"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62219"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000114"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501532"}],"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.62898","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62898","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:42:58Z","timestamp":1708497778000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,15]]},"references-count":15,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/ajmg.a.62898"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62898","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,15]]},"assertion":[{"value":"2021-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}