Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice

Autores
Bademci, Guney; Lachgar Ruiz, María; Deokar, Mangesh; Zafeer, Mohammad Faraz; Abad, Clemer; Baylan, Muzeyyen Yildirim; Ingham, Neil J.; Chen, Jing; Sineni, Claire J.; Vadgama, Nirmal; Karakikes, Ioannis; Guo, Shengru; Duman, Duygu; Singh, Nitu; Harlalka, Gaurav; Jain, Shirish P.; Chioza, Barry A.; Walz, Katherina; Steel, Karen P.; Nasir, Jamal; Tekin, Mustafa
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Bademci, Guney. University of Miami; Estados Unidos
Fil: Lachgar Ruiz, María. University College London; Estados Unidos
Fil: Deokar, Mangesh. No especifíca;
Fil: Zafeer, Mohammad Faraz. University of Miami; Estados Unidos
Fil: Abad, Clemer. University of Miami; Estados Unidos
Fil: Baylan, Muzeyyen Yildirim. No especifíca;
Fil: Ingham, Neil J.. University College London; Estados Unidos
Fil: Chen, Jing. University College London; Estados Unidos
Fil: Sineni, Claire J.. University of Miami; Estados Unidos
Fil: Vadgama, Nirmal. University of Stanford; Estados Unidos
Fil: Karakikes, Ioannis. University of Stanford; Estados Unidos
Fil: Guo, Shengru. University of Miami; Estados Unidos
Fil: Duman, Duygu. No especifíca;
Fil: Singh, Nitu. Oriental University; India
Fil: Harlalka, Gaurav. Rajarshi Shahu College Of Pharmacy; India
Fil: Jain, Shirish P.. No especifíca;
Fil: Chioza, Barry A.. University of Exeter; Reino Unido
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
Fil: Steel, Karen P.. University College London; Estados Unidos
Fil: Nasir, Jamal. University Of Northampton; Reino Unido
Fil: Tekin, Mustafa. University of Miami; Estados Unidos
Materia
AUTOSOMAL RECESSIVE
DEAFNESS
HEARING LOSS
MINAR2
NOTCH2
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/214462
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/214462
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and miceBademci, GuneyLachgar Ruiz, MaríaDeokar, MangeshZafeer, Mohammad FarazAbad, ClemerBaylan, Muzeyyen YildirimIngham, Neil J.Chen, JingSineni, Claire J.Vadgama, NirmalKarakikes, IoannisGuo, ShengruDuman, DuyguSingh, NituHarlalka, GauravJain, Shirish P.Chioza, Barry A.Walz, KatherinaSteel, Karen P.Nasir, JamalTekin, MustafaAUTOSOMAL RECESSIVEDEAFNESSHEARING LOSSMINAR2NOTCH2https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Discovery 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.Fil: Bademci, Guney. University of Miami; Estados UnidosFil: Lachgar Ruiz, María. University College London; Estados UnidosFil: Deokar, Mangesh. No especifíca;Fil: Zafeer, Mohammad Faraz. University of Miami; Estados UnidosFil: Abad, Clemer. University of Miami; Estados UnidosFil: Baylan, Muzeyyen Yildirim. No especifíca;Fil: Ingham, Neil J.. University College London; Estados UnidosFil: Chen, Jing. University College London; Estados UnidosFil: Sineni, Claire J.. University of Miami; Estados UnidosFil: Vadgama, Nirmal. University of Stanford; Estados UnidosFil: Karakikes, Ioannis. University of Stanford; Estados UnidosFil: Guo, Shengru. University of Miami; Estados UnidosFil: Duman, Duygu. No especifíca;Fil: Singh, Nitu. Oriental University; IndiaFil: Harlalka, Gaurav. Rajarshi Shahu College Of Pharmacy; IndiaFil: Jain, Shirish P.. No especifíca;Fil: Chioza, Barry A.. University of Exeter; Reino UnidoFil: 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; ArgentinaFil: Steel, Karen P.. University College London; Estados UnidosFil: Nasir, Jamal. University Of Northampton; Reino UnidoFil: Tekin, Mustafa. University of Miami; Estados UnidosNational Academy of Sciences2022-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/214462Bademci, 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; 1-110027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2204084119info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:00Zoai:ri.conicet.gov.ar:11336/214462instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:56:00.662CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
title Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
spellingShingle Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
Bademci, Guney
AUTOSOMAL RECESSIVE
DEAFNESS
HEARING LOSS
MINAR2
NOTCH2
title_short Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
title_full Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
title_fullStr Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
title_full_unstemmed Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
title_sort Mutations in MINAR2 encoding membrane integral NOTCH2-associated receptor 2 cause deafness in humans and mice
dc.creator.none.fl_str_mv Bademci, Guney
Lachgar Ruiz, María
Deokar, Mangesh
Zafeer, Mohammad Faraz
Abad, Clemer
Baylan, Muzeyyen Yildirim
Ingham, Neil J.
Chen, Jing
Sineni, Claire J.
Vadgama, Nirmal
Karakikes, Ioannis
Guo, Shengru
Duman, Duygu
Singh, Nitu
Harlalka, Gaurav
Jain, Shirish P.
Chioza, Barry A.
Walz, Katherina
Steel, Karen P.
Nasir, Jamal
Tekin, Mustafa
author Bademci, Guney
author_facet Bademci, Guney
Lachgar Ruiz, María
Deokar, Mangesh
Zafeer, Mohammad Faraz
Abad, Clemer
Baylan, Muzeyyen Yildirim
Ingham, Neil J.
Chen, Jing
Sineni, Claire J.
Vadgama, Nirmal
Karakikes, Ioannis
Guo, Shengru
Duman, Duygu
Singh, Nitu
Harlalka, Gaurav
Jain, Shirish P.
Chioza, Barry A.
Walz, Katherina
Steel, Karen P.
Nasir, Jamal
Tekin, Mustafa
author_role author
author2 Lachgar Ruiz, María
Deokar, Mangesh
Zafeer, Mohammad Faraz
Abad, Clemer
Baylan, Muzeyyen Yildirim
Ingham, Neil J.
Chen, Jing
Sineni, Claire J.
Vadgama, Nirmal
Karakikes, Ioannis
Guo, Shengru
Duman, Duygu
Singh, Nitu
Harlalka, Gaurav
Jain, Shirish P.
Chioza, Barry A.
Walz, Katherina
Steel, Karen P.
Nasir, Jamal
Tekin, Mustafa
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AUTOSOMAL RECESSIVE
DEAFNESS
HEARING LOSS
MINAR2
NOTCH2
topic AUTOSOMAL RECESSIVE
DEAFNESS
HEARING LOSS
MINAR2
NOTCH2
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Bademci, Guney. University of Miami; Estados Unidos
Fil: Lachgar Ruiz, María. University College London; Estados Unidos
Fil: Deokar, Mangesh. No especifíca;
Fil: Zafeer, Mohammad Faraz. University of Miami; Estados Unidos
Fil: Abad, Clemer. University of Miami; Estados Unidos
Fil: Baylan, Muzeyyen Yildirim. No especifíca;
Fil: Ingham, Neil J.. University College London; Estados Unidos
Fil: Chen, Jing. University College London; Estados Unidos
Fil: Sineni, Claire J.. University of Miami; Estados Unidos
Fil: Vadgama, Nirmal. University of Stanford; Estados Unidos
Fil: Karakikes, Ioannis. University of Stanford; Estados Unidos
Fil: Guo, Shengru. University of Miami; Estados Unidos
Fil: Duman, Duygu. No especifíca;
Fil: Singh, Nitu. Oriental University; India
Fil: Harlalka, Gaurav. Rajarshi Shahu College Of Pharmacy; India
Fil: Jain, Shirish P.. No especifíca;
Fil: Chioza, Barry A.. University of Exeter; Reino Unido
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
Fil: Steel, Karen P.. University College London; Estados Unidos
Fil: Nasir, Jamal. University Of Northampton; Reino Unido
Fil: Tekin, Mustafa. University of Miami; Estados Unidos
description 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.
publishDate 2022
dc.date.none.fl_str_mv 2022-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/214462
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
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/214462
identifier_str_mv 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
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.2204084119
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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