{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:58:18Z","timestamp":1778633898369,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"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":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple congenital contractures (MCC) comprise a number of rare, non\u2010progressive conditions displaying marked phenotypic and etiologic heterogeneity. A genetic cause can be established in approximately half of the affected individuals, attributed to genetic defects in the formation and functioning of the central and peripheral nervous system, neuromuscular junctions, skeletal muscles, and connective tissue. Ubiquitin\u2010specific protease 14 (\n                    <jats:italic>USP14<\/jats:italic>\n                    ) encodes a major proteasome\u2010associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis.\n                    <jats:italic>Usp14<\/jats:italic>\n                    \u2010deficient mice show a phenotype similar to lethal human MCC phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. We describe a new, autosomal recessive MCC phenotype in three fetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4\u2010bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11, SCV002028347) in\n                    <jats:italic>USP14<\/jats:italic>\n                    , and sequencing of family members showed segregation with the phenotype. RT\u2010qPCR experiment in an unaffected heterozygote revealed that mutant\n                    <jats:italic>USP14<\/jats:italic>\n                    was expressed, indicating that abnormal transcript escapes nonsense\u2010mediated mRNA decay. We propose that herein described fetuses represent the first human phenotype of\n                    <jats:italic>USP14<\/jats:italic>\n                    loss, with callosal anomalies and\/or cortical malformations, multiple contractures, and recognizable dysmorphic facial features.\n                  <\/jats:p>","DOI":"10.1111\/cge.14117","type":"journal-article","created":{"date-parts":[[2022,1,23]],"date-time":"2022-01-23T06:53:57Z","timestamp":1642920837000},"page":"421-428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional loss of ubiquitin\u2010specific protease 14 may lead to a novel distal arthrogryposis phenotype"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-6431","authenticated-orcid":false,"given":"Gozde Tutku","family":"Turgut","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3172-5368","authenticated-orcid":false,"given":"Umut","family":"Altunoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"},{"name":"Department of Medical Genetics Ko\u00e7 University School of Medicine (KUSoM)  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tugba Sarac","family":"Sivrikoz","sequence":"additional","affiliation":[{"name":"Perinatology Unit, Department of Obstetrics and Gynecology, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guven","family":"Toksoy","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tu\u011fba","family":"Kalayc\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u015eahin","family":"Avc\u0131","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"},{"name":"Department of Medical Genetics Ko\u00e7 University School of Medicine (KUSoM)  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birsen","family":"Karaman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"},{"name":"Department of Pediatric Basic Sciences, Institute of Child Health Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cagri","family":"Gulec","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seher","family":"Ba\u015faran","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6zde Ye\u015fil","family":"Say\u0131n","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-499X","authenticated-orcid":false,"given":"Hulya","family":"Kayserili","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul Turkey"},{"name":"Department of Medical Genetics Ko\u00e7 University School of Medicine (KUSoM)  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-4338","authenticated-orcid":false,"given":"Zehra Oya","family":"Uyguner","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Istanbul Medical Faculty Istanbul University  Istanbul 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