Publication:
Functional loss of ubiquitin-specific protease 14 may lead to a novel distal arthrogryposis phenotype

dc.contributor.coauthorTurgut, Gozde Tutku
dc.contributor.coauthorSivrikoz, Tugba Sarac
dc.contributor.coauthorToksoy, Guven
dc.contributor.coauthorKalayci, Tugba
dc.contributor.coauthorKaraman, Birsen
dc.contributor.coauthorGulec, Cagri
dc.contributor.coauthorBasaran, Seher
dc.contributor.coauthorSayin, Gozde Yesil
dc.contributor.coauthorUyguner, Zehra Oya
dc.contributor.departmentKUH (Koç University Hospital)
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorAltunoğlu, Umut
dc.contributor.kuauthorAvcı, Şahin
dc.contributor.kuauthorKayserili, Hülya
dc.contributor.schoolcollegeinstituteKUH (KOÇ UNIVERSITY HOSPITAL)
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-10T00:12:04Z
dc.date.issued2022
dc.description.abstractMultiple congenital contractures (MCC) comprise a number of rare, non-progressive 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-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient 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-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11, SCV002028347) in USP14, and sequencing of family members showed segregation with the phenotype. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay. We propose that herein described fetuses represent the first human phenotype of USP14 loss, with callosal anomalies and/or cortical malformations, multiple contractures, and recognizable dysmorphic facial features.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue4
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipScientific Research Projects Coordination Unit of Istanbul University [37765] Scientific Research Projects Coordination Unit of Istanbul University (Project ID 37765)
dc.description.volume101
dc.identifier.doi10.1111/cge.14117
dc.identifier.eissn1399-0004
dc.identifier.issn0009-9163
dc.identifier.quartileQ2
dc.identifier.scopus2-s2.0-85123957150
dc.identifier.urihttps://doi.org/10.1111/cge.14117
dc.identifier.urihttps://hdl.handle.net/20.500.14288/17569
dc.identifier.wos748785500001
dc.keywordsArthrogryposis
dc.keywordsExome sequencing
dc.keywordsMultiple congenital contractures
dc.keywordsUbiquitins
dc.keywordsUsp14
dc.keywordsMutations
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofClinical Genetics
dc.subjectGenetics
dc.subjectHeredity
dc.titleFunctional loss of ubiquitin-specific protease 14 may lead to a novel distal arthrogryposis phenotype
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorAltunoğlu, Umut
local.contributor.kuauthorAvcı, Şahin
local.contributor.kuauthorKayserili, Hülya
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit1KUH (KOÇ UNIVERSITY HOSPITAL)
local.publication.orgunit2KUH (Koç University Hospital)
local.publication.orgunit2School of Medicine
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