Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2

Fecha de publicación: 01/07/2021 Fecha Ahead of Print: 01/07/2021

Autores de IIS La Fe

Gema García García

Autor
José María Millán Salvador

Autor

Participantes ajenos a IIS La Fe

Stemerdink M
García-Bohórquez B
Schellens R
Van Wijk E

Grupos

Biomedicina Molecular, Celular y Genómica

Leader

José María Millán Salvador
Unidad mixta de investigación en enfermedades raras (CIPF)

Leader

José María Millán Salvador

Abstract

Usher syndrome (USH) is a rare, autosomal recessively inherited disorder resulting in a combination of sensorineural hearing loss and a progressive loss of vision resulting from retinitis pigmentosa (RP), occasionally accompanied by an altered vestibular function. More and more evidence is building up indicating that also sleep deprivation, olfactory dysfunction, deficits in tactile perception and reduced sperm motility are part of the disease etiology. USH can be clinically classified into three different types, of which Usher syndrome type 2 (USH2) is the most prevalent. In this review, we, therefore, assess the genetic and clinical aspects, available models and therapeutic developments for USH2. Mutations in USH2A, ADGRV1 and WHRN have been described to be responsible for USH2, with USH2A being the most frequently mutated USH-associated gene, explaining 50% of all cases. The proteins encoded by the USH2 genes together function in a dynamic protein complex that, among others, is found at the photoreceptor periciliary membrane and at the base of the hair bundles of inner ear hair cells. To unravel the pathogenic mechanisms underlying USH2, patient-derived cellular models and animal models including mouse, zebrafish and drosophila, have been generated that all in part mimic the USH phenotype. Multiple cellular and genetic therapeutic approaches are currently under development for USH2, mainly focused on preserving or partially restoring the visual function of which one is already in the clinical phase. These developments are opening a new gate towards a possible treatment for USH2 patients.

Datos de la publicación

ISSN/ISSNe:: 0340-6717, 1432-1203
Tipo:: Article
Páginas:: 737-758
DOI:: 10.1007/s00439-021-02324-w
Factor de Impacto:: 1,850 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

No hay documentos

Métricas

Filiaciones

Stemerdink M:: #Contributed equally.

1Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
García-Bohórquez B:: #Contributed equally.

1Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.

Instituto de Investigación. 2Grupo de Investigación en Biomedicina Molecular, Celular y Genómica Health Research Institute La Fe, Valencia, Spain.

Grupo de Investigación en Biomedicina Molecular, Celular y Genómica Health Research Institute La Fe, Valencia, Spain

CIBERER, Madrid, Spain
Schellens R:: #Contributed equally.

1Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
Garcia-Garcia G:: #Contributed equally.

Instituto de Investigación. 2Grupo de Investigación en Biomedicina Molecular, Celular y Genómica Health Research Institute La Fe, Valencia, Spain.

3CIBERER, Madrid, Spain.

Grupo de Investigación en Biomedicina Molecular, Celular y Genómica Health Research Institute La Fe, Valencia, Spain

CIBERER, Madrid, Spain
Van Wijk E:: #Contributed equally.

1Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands.
Millan JM:: #Contributed equally.

Instituto de Investigación. 4Grupo de Investigación en Biomedicina Molecular, Celular y Genómica Health Research Institute La Fe, Valencia, Spain.

5CIBERER, Madrid, Spain.

Grupo de Investigación en Biomedicina Molecular, Celular y Genómica Health Research Institute La Fe, Valencia, Spain.

CIBERER, Madrid, Spain.

Keywords

PROTEIN-COUPLED RECEPTOR; SYNDROME TYPE IIA; ANKLE-LINK COMPLEX; VISUAL-FIELD LOSS; HEARING-LOSS; RETINITIS-PIGMENTOSA; USH2A GENE; MOUSE MODEL; AUDIOGENIC-SEIZURES; CARRYING MUTATIONS

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