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

Fecha de publicación: 18/03/2020 Fecha Ahead of Print: 18/03/2020

Autores de IIS La Fe

Gema García García

Autor
Elena María Aller Mañas

Autor
Teresa Jaijo Sanchís

Autor
Carla Fuster García

Autor
Ana Rodríguez Muñóz

Autor
José María Millán Salvador

Autor

Participantes ajenos a IIS La Fe

Sanchez-Navarro, Iker
Vallejo, Elena
Telleria, JJ
Vazquez, Selma
Beltran, Sergi
Derdak, Sophia
Zurita, Olga
Villaverde-Montero, Cristina
Avila-Fernandez, Almudena
Corton, Marta
Blanco-Kelly, Fiona
Hakonarson, Hakon
Ayuso, Carmen

Grupos

Abstract

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.

Datos de la publicación

ISSN/ISSNe:: 1090-0535, 1090-0535
Tipo:: Article
Páginas:: 216-225
DOI:
Factor de Impacto:: 0,891 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Métricas

Filiaciones

Garcia-Garcia, Gema:: Instituto de Investigación. Inst La Fe IIS La Fe, Res Grp Mol Cellular & Genom Biomed Hlth Res, Valencia, Spain

Instituto de Investigación. Mixed Unit Rare Dis IIS La Fe CIPF, Valencia, Spain

Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain
Sanchez-Navarro, Iker:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain
Aller, Elena:: Instituto de Investigación. Inst La Fe IIS La Fe, Res Grp Mol Cellular & Genom Biomed Hlth Res, Valencia, Spain

Instituto de Investigación. Mixed Unit Rare Dis IIS La Fe CIPF, Valencia, Spain

Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

La Fe Univ Hosp, Genet Unit, Valencia, Spain
Jaijo, Teresa:: Instituto de Investigación. Inst La Fe IIS La Fe, Res Grp Mol Cellular & Genom Biomed Hlth Res, Valencia, Spain

Instituto de Investigación. Mixed Unit Rare Dis IIS La Fe CIPF, Valencia, Spain

Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

La Fe Univ Hosp, Genet Unit, Valencia, Spain
Fuster-Garcia, Carla:: Instituto de Investigación. Inst La Fe IIS La Fe, Res Grp Mol Cellular & Genom Biomed Hlth Res, Valencia, Spain

Instituto de Investigación. Mixed Unit Rare Dis IIS La Fe CIPF, Valencia, Spain
Rodriguez-Munoz, Ana:: Instituto de Investigación. Inst La Fe IIS La Fe, Res Grp Mol Cellular & Genom Biomed Hlth Res, Valencia, Spain

Instituto de Investigación. Mixed Unit Rare Dis IIS La Fe CIPF, Valencia, Spain
Vallejo, Elena:: Medina del Campo Hosp, Dept Ophthalmol, Valladolid, Spain
Telleria, JJ:: Univ Valladolid, IBGM, Valladolid, Spain
Vazquez, Selma:: Univ Hosp Valladolid, Valladolid, Spain
Beltran, Sergi:: Natl Ctr Genom Anal CNAG CRG Ctr Genom Regulat, Barcelona, Spain
Derdak, Sophia:: Natl Ctr Genom Anal CNAG CRG Ctr Genom Regulat, Barcelona, Spain
Zurita, Olga:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain
Villaverde-Montero, Cristina:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain
Avila-Fernandez, Almudena:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain
Corton, Marta:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain
Blanco-Kelly, Fiona:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain
Hakonarson, Hakon:: Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA
aillan, JM:: Instituto de Investigación. Inst La Fe IIS La Fe, Res Grp Mol Cellular & Genom Biomed Hlth Res, Valencia, Spain

Instituto de Investigación. Mixed Unit Rare Dis IIS La Fe CIPF, Valencia, Spain

Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain
Ayuso, Carmen:: Ctr Biomed Res Rare Dis CIBERER, Madrid, Spain

UAM, IIS Fdn Jimenez Diaz Univ Hosp IIS FJD, Dept Genet, Madrid, Spain

Keywords

PEROXISOME BIOGENESIS DISORDERS; HEIMLER SYNDROME; PATIENT

Proyectos asociados

CARACTERIZACION MOLECULAR DE PACIENTES CON SINDROME DE USHER. ESTUDIO DE LOS GENES RESPONSABLES: CDH23 Y PCDH15 Y CANDIDATOS: WHRN, CXADR Y PDZK7

Investigador Principal: JOSÉ MARÍA MILLÁN SALVADOR

PI07/0558 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2008

MOLECULAR MAECHANISMS OF RETINAL DEGENERATION IN HUMANS WITH RETINITIS PIGMENTOSA. ROLE OF INFLAMMATION, OXIDATIVE STRESS AND GLIAL ACTIVATION

CP09/00118 (MIGUEL SERVET) . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

CARACTERIZACION MOLECULAR EN PACIENTES CON SINDROME DE USHER TIPO I MEDIANTE LA APLICACION DE LAS TECNICAS DE SECUENCIACION Y CGH-ARRAY EN GENES RESPONSABLES Y GENES CANDIDATOS

FPU_AP2009-3344 . MINISTERIO DE EDUCACION, CULTURA Y DEPORTE; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010