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Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment

PURPOSE: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. METHODS: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopath...

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Autores principales: García-García, Gema, Sanchez-Navarro, Iker, Aller, Elena, Jaijo, Teresa, Fuster-Garcia, Carla, Rodríguez-Munoz, Ana, Vallejo, Elena, Tellería, Juan José, Vázquez, Selma, Beltrán, Sergi, Derdak, Sophia, Zurita, Olga, Villaverde-Montero, Cristina, Avila-Fernández, Almudena, Corton, Marta, Blanco-Kelly, Fiona, Hakonarson, Hakon, Millán, José M., Ayuso, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Vision 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090270/
https://www.ncbi.nlm.nih.gov/pubmed/32214787
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author García-García, Gema
Sanchez-Navarro, Iker
Aller, Elena
Jaijo, Teresa
Fuster-Garcia, Carla
Rodríguez-Munoz, Ana
Vallejo, Elena
Tellería, Juan José
Vázquez, Selma
Beltrán, Sergi
Derdak, Sophia
Zurita, Olga
Villaverde-Montero, Cristina
Avila-Fernández, Almudena
Corton, Marta
Blanco-Kelly, Fiona
Hakonarson, Hakon
Millán, José M.
Ayuso, Carmen
author_facet García-García, Gema
Sanchez-Navarro, Iker
Aller, Elena
Jaijo, Teresa
Fuster-Garcia, Carla
Rodríguez-Munoz, Ana
Vallejo, Elena
Tellería, Juan José
Vázquez, Selma
Beltrán, Sergi
Derdak, Sophia
Zurita, Olga
Villaverde-Montero, Cristina
Avila-Fernández, Almudena
Corton, Marta
Blanco-Kelly, Fiona
Hakonarson, Hakon
Millán, José M.
Ayuso, Carmen
author_sort García-García, Gema
collection PubMed
description PURPOSE: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. METHODS: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. RESULTS: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf–blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. CONCLUSIONS: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness–blindness association.
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spelling pubmed-70902702020-03-25 Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment García-García, Gema Sanchez-Navarro, Iker Aller, Elena Jaijo, Teresa Fuster-Garcia, Carla Rodríguez-Munoz, Ana Vallejo, Elena Tellería, Juan José Vázquez, Selma Beltrán, Sergi Derdak, Sophia Zurita, Olga Villaverde-Montero, Cristina Avila-Fernández, Almudena Corton, Marta Blanco-Kelly, Fiona Hakonarson, Hakon Millán, José M. Ayuso, Carmen Mol Vis Research Article PURPOSE: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. METHODS: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. RESULTS: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf–blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. CONCLUSIONS: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness–blindness association. Molecular Vision 2020-03-18 /pmc/articles/PMC7090270/ /pubmed/32214787 Text en Copyright © 2020 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.
spellingShingle Research Article
García-García, Gema
Sanchez-Navarro, Iker
Aller, Elena
Jaijo, Teresa
Fuster-Garcia, Carla
Rodríguez-Munoz, Ana
Vallejo, Elena
Tellería, Juan José
Vázquez, Selma
Beltrán, Sergi
Derdak, Sophia
Zurita, Olga
Villaverde-Montero, Cristina
Avila-Fernández, Almudena
Corton, Marta
Blanco-Kelly, Fiona
Hakonarson, Hakon
Millán, José M.
Ayuso, Carmen
Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment
title Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment
title_full Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment
title_fullStr Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment
title_full_unstemmed Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment
title_short Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment
title_sort exome sequencing identifies pex6 mutations in three cases diagnosed with retinitis pigmentosa and hearing impairment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090270/
https://www.ncbi.nlm.nih.gov/pubmed/32214787
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