Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/23770
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dc.contributor.authorSeco, Celia Zazo
dc.contributor.authorOonk, Anne M M
dc.contributor.authorDomínguez-Ruiz, María
dc.contributor.authorDraaisma, Jos M T
dc.contributor.authorGandía, Marta
dc.contributor.authorOostrik, Jaap
dc.contributor.authorNeveling, Kornelia
dc.contributor.authorKunst, Henricus P M
dc.contributor.authorHoefsloot, Lies H
dc.contributor.authordel Castillo, Ignacio
dc.contributor.authorPennings, Ronald J E
dc.contributor.authorKremer, Hannie
dc.contributor.authorAdmiraal, Ronald J C
dc.contributor.authorSchraders, Margit
dc.date.accessioned2019-06-28T13:59:34Z-
dc.date.available2019-06-28T13:59:34Z-
dc.date.issued2015-02
dc.identifier.citationEur. J. Hum. Genet..2015 Feb;(23)2:189-94
dc.identifier.urihttps://hdl.handle.net/20.500.12530/23770-
dc.description.abstractIn a consanguineous Turkish family diagnosed with autosomal recessive nonsyndromic hearing impairment (arNSHI), a homozygous region of 47.4 Mb was shared by the two affected siblings on chromosome 6p21.1-q15. This region contains 247 genes including the known deafness gene MYO6. No pathogenic variants were found in MYO6, neither with sequence analysis of the coding region and splice sites nor with mRNA analysis. Subsequent candidate gene evaluation revealed CLIC5 as an excellent candidate gene. The orthologous mouse gene is mutated in the jitterbug mutant that exhibits progressive hearing impairment and vestibular dysfunction. Mutation analysis of CLIC5 revealed a homozygous nonsense mutation c.96T>A (p.(Cys32Ter)) that segregated with the hearing loss. Further analysis of CLIC5 in 213 arNSHI patients from mostly Dutch and Spanish origin did not reveal any additional pathogenic variants. CLIC5 mutations are thus not a common cause of arNSHI in these populations. The hearing loss in the present family had an onset in early childhood and progressed from mild to severe or even profound before the second decade. Impaired hearing is accompanied by vestibular areflexia and in one of the patients with mild renal dysfunction. Although we demonstrate that CLIC5 is expressed in many other human tissues, no additional symptoms were observed in these patients. In conclusion, our results show that CLIC5 is a novel arNSHI gene involved in progressive hearing impairment, vestibular and possibly mild renal dysfunction in a family of Turkish origin.
dc.language.isoeng
dc.rightsopenAccess-
dc.subject.meshAdolescent
dc.subject.meshCell Line
dc.subject.meshChild
dc.subject.meshChloride Channels
dc.subject.meshDeafness
dc.subject.meshFemale
dc.subject.meshHumans
dc.subject.meshInfant
dc.subject.meshMale
dc.subject.meshMicrofilament Proteins
dc.subject.meshNonsense Mediated mRNA Decay
dc.subject.meshPedigree
dc.subject.meshRNA, Messenger
dc.subject.meshVestibular Diseases
dc.subject.meshCodon, Nonsense
dc.subject.meshHomozygote
dc.titleProgressive hearing loss and vestibular dysfunction caused by a homozygous nonsense mutation in CLIC5.
dc.typeArtículo
dc.identifier.pubmedID24781754
dc.format.volume23
dc.format.page189-94
dc.identifier.e-issn1476-5438
dc.identifier.journalEuropean journal of human genetics : EJHG
dc.identifier.doi10.1038/ejhg.2014.83
dc.format.number2
dc.identifier.pmcPMC4297911
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. Ramón y Cajal > Artículos

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