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Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder

Pathogenic variants in the PJVK gene cause the DFNB59 type of autosomal recessive non-syndromic hearing impairment (AR-NSHI). Phenotypes are not homogeneous, as a few subjects show auditory neuropathy spectrum disorder (ANSD), while others show cochlear hearing loss. The numbers of reported cases an...

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Autores principales: Domínguez-Ruiz, María, Rodríguez-Ballesteros, Montserrat, Gandía, Marta, Gómez-Rosas, Elena, Villamar, Manuela, Scimemi, Pietro, Mancini, Patrizia, Rendtorff, Nanna D., Moreno-Pelayo, Miguel A., Tranebjaerg, Lisbeth, Medà, Carme, Santarelli, Rosamaria, del Castillo, Ignacio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775161/
https://www.ncbi.nlm.nih.gov/pubmed/35052489
http://dx.doi.org/10.3390/genes13010149
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author Domínguez-Ruiz, María
Rodríguez-Ballesteros, Montserrat
Gandía, Marta
Gómez-Rosas, Elena
Villamar, Manuela
Scimemi, Pietro
Mancini, Patrizia
Rendtorff, Nanna D.
Moreno-Pelayo, Miguel A.
Tranebjaerg, Lisbeth
Medà, Carme
Santarelli, Rosamaria
del Castillo, Ignacio
author_facet Domínguez-Ruiz, María
Rodríguez-Ballesteros, Montserrat
Gandía, Marta
Gómez-Rosas, Elena
Villamar, Manuela
Scimemi, Pietro
Mancini, Patrizia
Rendtorff, Nanna D.
Moreno-Pelayo, Miguel A.
Tranebjaerg, Lisbeth
Medà, Carme
Santarelli, Rosamaria
del Castillo, Ignacio
author_sort Domínguez-Ruiz, María
collection PubMed
description Pathogenic variants in the PJVK gene cause the DFNB59 type of autosomal recessive non-syndromic hearing impairment (AR-NSHI). Phenotypes are not homogeneous, as a few subjects show auditory neuropathy spectrum disorder (ANSD), while others show cochlear hearing loss. The numbers of reported cases and pathogenic variants are still small to establish accurate genotype-phenotype correlations. We investigated a cohort of 77 Spanish familial cases of AR-NSHI, in whom DFNB1 had been excluded, and a cohort of 84 simplex cases with isolated ANSD in whom OTOF variants had been excluded. All seven exons and exon-intron boundaries of the PJVK gene were sequenced. We report three novel DFNB59 cases, one from the AR-NSHI cohort and two from the ANSD cohort, with stable, severe to profound NSHI. Two of the subjects received unilateral cochlear implantation, with apparent good outcomes. Our study expands the spectrum of PJVK mutations, as we report four novel pathogenic variants: p.Leu224Arg, p.His294Ilefs*43, p.His294Asp and p.Phe317Serfs*20. We review the reported cases of DFNB59, summarize the clinical features of this rare subtype of AR-NSHI and discuss the involvement of PJVK in ANSD.
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spelling pubmed-87751612022-01-21 Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder Domínguez-Ruiz, María Rodríguez-Ballesteros, Montserrat Gandía, Marta Gómez-Rosas, Elena Villamar, Manuela Scimemi, Pietro Mancini, Patrizia Rendtorff, Nanna D. Moreno-Pelayo, Miguel A. Tranebjaerg, Lisbeth Medà, Carme Santarelli, Rosamaria del Castillo, Ignacio Genes (Basel) Article Pathogenic variants in the PJVK gene cause the DFNB59 type of autosomal recessive non-syndromic hearing impairment (AR-NSHI). Phenotypes are not homogeneous, as a few subjects show auditory neuropathy spectrum disorder (ANSD), while others show cochlear hearing loss. The numbers of reported cases and pathogenic variants are still small to establish accurate genotype-phenotype correlations. We investigated a cohort of 77 Spanish familial cases of AR-NSHI, in whom DFNB1 had been excluded, and a cohort of 84 simplex cases with isolated ANSD in whom OTOF variants had been excluded. All seven exons and exon-intron boundaries of the PJVK gene were sequenced. We report three novel DFNB59 cases, one from the AR-NSHI cohort and two from the ANSD cohort, with stable, severe to profound NSHI. Two of the subjects received unilateral cochlear implantation, with apparent good outcomes. Our study expands the spectrum of PJVK mutations, as we report four novel pathogenic variants: p.Leu224Arg, p.His294Ilefs*43, p.His294Asp and p.Phe317Serfs*20. We review the reported cases of DFNB59, summarize the clinical features of this rare subtype of AR-NSHI and discuss the involvement of PJVK in ANSD. MDPI 2022-01-15 /pmc/articles/PMC8775161/ /pubmed/35052489 http://dx.doi.org/10.3390/genes13010149 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Domínguez-Ruiz, María
Rodríguez-Ballesteros, Montserrat
Gandía, Marta
Gómez-Rosas, Elena
Villamar, Manuela
Scimemi, Pietro
Mancini, Patrizia
Rendtorff, Nanna D.
Moreno-Pelayo, Miguel A.
Tranebjaerg, Lisbeth
Medà, Carme
Santarelli, Rosamaria
del Castillo, Ignacio
Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder
title Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder
title_full Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder
title_fullStr Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder
title_full_unstemmed Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder
title_short Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder
title_sort novel pathogenic variants in pjvk, the gene encoding pejvakin, in subjects with autosomal recessive non-syndromic hearing impairment and auditory neuropathy spectrum disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775161/
https://www.ncbi.nlm.nih.gov/pubmed/35052489
http://dx.doi.org/10.3390/genes13010149
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