Mostrar el registro sencillo del ítem
dc.contributor.author
Bademci, Guney
dc.contributor.author
Lachgar Ruiz, María
dc.contributor.author
Deokar, Mangesh
dc.contributor.author
Zafeer, Mohammad Faraz
dc.contributor.author
Abad, Clemer
dc.contributor.author
Baylan, Muzeyyen Yildirim
dc.contributor.author
Ingham, Neil J.
dc.contributor.author
Chen, Jing
dc.contributor.author
Sineni, Claire J.
dc.contributor.author
Vadgama, Nirmal
dc.contributor.author
Karakikes, Ioannis
dc.contributor.author
Guo, Shengru
dc.contributor.author
Duman, Duygu
dc.contributor.author
Singh, Nitu
dc.contributor.author
Harlalka, Gaurav
dc.contributor.author
Jain, Shirish P.
dc.contributor.author
Chioza, Barry A.
dc.contributor.author
Walz, Katherina
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Steel, Karen P.
dc.contributor.author
Nasir, Jamal
dc.contributor.author
Tekin, Mustafa
dc.date.available
2023-10-09T12:08:31Z
dc.date.issued
2022-06
dc.identifier.citation
Bademci, Guney; Lachgar Ruiz, María; Deokar, Mangesh; Zafeer, Mohammad Faraz; Abad, Clemer; et al.; Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 119; 26; 6-2022; 1-11
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/214462
dc.description.abstract
Discovery of deafness genes and elucidating their functions have substantially contributed to our understanding of hearing physiology and its pathologies. Here we report on DNA variants in MINAR2, encoding membrane integral NOTCH2-associated receptor 2, in four families underlying autosomal recessive nonsyndromic deafness. Neurologic evaluation of affected individuals at ages ranging from 4 to 80 y old does not show additional abnormalities. MINAR2 is a recently annotated gene with limited functional understanding. We detected three MINAR2 variants, c.144G > A (p.Trp48*), c.412_419delCGGTTTTG (p.Arg138Valfs*10), and c.393G > T, in 13 individuals with congenital- or prelingual-onset severe-to-profound sensorineural hearing loss (HL). The c.393G > T variant is shown to disrupt a splice donor site. We show that Minar2 is expressed in the mouse inner ear, with the protein localizing mainly in the hair cells, spiral ganglia, the spiral limbus, and the stria vascularis. Mice with loss of function of the Minar2 protein (Minar2tm1b/tm1b) present with rapidly progressive sensorineural HL associated with a reduction in outer hair cell stereocilia in the shortest row and degeneration of hair cells at a later age. We conclude that MINAR2 is essential for hearing in humans and mice and its disruption leads to sensorineural HL. Progressive HL observed in mice and in some affected individuals and as well as relative preservation of hair cells provides an opportunity to interfere with HL using genetic therapies.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
AUTOSOMAL RECESSIVE
dc.subject
DEAFNESS
dc.subject
HEARING LOSS
dc.subject
MINAR2
dc.subject
NOTCH2
dc.subject.classification
Genética y Herencia
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-07-07T22:43:27Z
dc.journal.volume
119
dc.journal.number
26
dc.journal.pagination
1-11
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.description.fil
Fil: Bademci, Guney. University of Miami; Estados Unidos
dc.description.fil
Fil: Lachgar Ruiz, María. University College London; Estados Unidos
dc.description.fil
Fil: Deokar, Mangesh. No especifíca;
dc.description.fil
Fil: Zafeer, Mohammad Faraz. University of Miami; Estados Unidos
dc.description.fil
Fil: Abad, Clemer. University of Miami; Estados Unidos
dc.description.fil
Fil: Baylan, Muzeyyen Yildirim. No especifíca;
dc.description.fil
Fil: Ingham, Neil J.. University College London; Estados Unidos
dc.description.fil
Fil: Chen, Jing. University College London; Estados Unidos
dc.description.fil
Fil: Sineni, Claire J.. University of Miami; Estados Unidos
dc.description.fil
Fil: Vadgama, Nirmal. University of Stanford; Estados Unidos
dc.description.fil
Fil: Karakikes, Ioannis. University of Stanford; Estados Unidos
dc.description.fil
Fil: Guo, Shengru. University of Miami; Estados Unidos
dc.description.fil
Fil: Duman, Duygu. No especifíca;
dc.description.fil
Fil: Singh, Nitu. Oriental University; India
dc.description.fil
Fil: Harlalka, Gaurav. Rajarshi Shahu College Of Pharmacy; India
dc.description.fil
Fil: Jain, Shirish P.. No especifíca;
dc.description.fil
Fil: Chioza, Barry A.. University of Exeter; Reino Unido
dc.description.fil
Fil: Walz, Katherina. Miami University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Steel, Karen P.. University College London; Estados Unidos
dc.description.fil
Fil: Nasir, Jamal. University Of Northampton; Reino Unido
dc.description.fil
Fil: Tekin, Mustafa. University of Miami; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.2204084119
Archivos asociados