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Whole exome sequencing identifies TRIOBP pathogenic variants as a cause of post-lingual bilateral moderate-to-severe sensorineural hearing loss.
Pollak, Agnieszka; Lechowicz, Urszula; Murcia Pienkowski, Victor Abel; Stawinski, Piotr; Kosinska, Joanna; Skarzynski, Henryk; Oldak, Monika; Ploski, Rafal.
Afiliação
  • Pollak A; Department of Genetics, Institute of Physiology and Pathology of Hearing, Mochnackiego 10, Warsaw, 02-042, Poland.
  • Lechowicz U; Department of Genetics, Institute of Physiology and Pathology of Hearing, Mochnackiego 10, Warsaw, 02-042, Poland.
  • Murcia Pienkowski VA; Department of Medical Genetics, Warsaw Medical University, Pawinskiego 3c, Warsaw, 02-106, Poland.
  • Stawinski P; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
  • Kosinska J; Department of Genetics, Institute of Physiology and Pathology of Hearing, Mochnackiego 10, Warsaw, 02-042, Poland.
  • Skarzynski H; Department of Medical Genetics, Warsaw Medical University, Pawinskiego 3c, Warsaw, 02-106, Poland.
  • Oldak M; Oto-Rhino-Laryngology Surgery Clinic, Institute of Physiology and Pathology of Hearing, Warsaw/Kajetany, Poland.
  • Ploski R; Department of Genetics, Institute of Physiology and Pathology of Hearing, Mochnackiego 10, Warsaw, 02-042, Poland. m.oldak@ifps.org.pl.
BMC Med Genet ; 18(1): 142, 2017 12 02.
Article em En | MEDLINE | ID: mdl-29197352
BACKGROUND: Implementation of whole exome sequencing has provided unique opportunity for a wide screening of causative variants in genetically heterogeneous diseases, including nonsyndromic hearing impairment. TRIOBP in the inner ear is responsible for proper structure and function of stereocilia and is necessary for sound transduction. METHODS: Whole exome sequencing followed by Sanger sequencing was conducted on patients derived from Polish hearing loss family. RESULTS: Based on whole exome analysis, we identified two TRIOBP pathogenic variants (c.802_805delCAGG, p.Gln268Leufs*610 and c.5014G>T, p.Gly1672*, the first of which was novel) causative of nonsyndromic, peri- to postlingual, moderate-to-severe hearing loss in three siblings from a Polish family. Typically, TRIOBP pathogenic variants lead to prelingual, severe-to-profound hearing loss, thus the onset and degree of hearing impairment in our patients represent a distinct phenotypic manifestation caused by TRIOBP variants. The pathogenic variant p.Gln268Leufs*610 disrupts the TRIOBP-4 and TRIOBP-5 isoforms (both expressed exclusively in the inner ear and retina) whereas the second pathogenic variant c.514G>T, p.Gly1672* affects only TRIOBP-5. CONCLUSIONS: The onset and degree of hearing impairment, characteristic for our patients, represent a unique phenotypic manifestation caused by TRIOBP pathogenic variants. Although TRIOBP alterations are not a frequent cause of hearing impairment, this gene should be thoroughly analyzed especially in patients with a postlingual hearing loss. A delayed onset of hearing impairment due to TRIOBP pathogenic variants creates a potential therapeutic window for future targeted therapies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Perda Auditiva Neurossensorial / Proteínas dos Microfilamentos / Mutação Tipo de estudo: Prognostic_studies Limite: Child / Child, preschool / Female / Humans / Male País/Região como assunto: Europa Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Perda Auditiva Neurossensorial / Proteínas dos Microfilamentos / Mutação Tipo de estudo: Prognostic_studies Limite: Child / Child, preschool / Female / Humans / Male País/Região como assunto: Europa Idioma: En Ano de publicação: 2017 Tipo de documento: Article