Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects

Autores
Domínguez Ruiz, María; Ruiz Palmero, Laura; Buonfiglio, Paula Inés; García Vaquero, Irene; Gómez Rosas, Irene; Goñi, Marina; Villamar, Manuela; Morín, Matías; Moreno Pelayo, Miguel A.; Elgoyhen, Ana Belen; Del Castillo, Francisco J.; Dalamon, Viviana Karina; Del Castillo, Ignacio
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.Keywords: non-syndromic hearing impairment; DFNB16; STRC; stereocilin; genetic epidemiology
Fil: Domínguez Ruiz, María. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Ruiz Palmero, Laura. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: García Vaquero, Irene. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Gómez Rosas, Irene. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Goñi, Marina. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Villamar, Manuela. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Morín, Matías. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Moreno Pelayo, Miguel A.. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Del Castillo, Francisco J.. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Del Castillo, Ignacio. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Materia
NON-SYNDROMIC HEARING IMPAIRMENT
DFNB16
STRC
STEREOCILIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/232752
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean SubjectsDomínguez Ruiz, MaríaRuiz Palmero, LauraBuonfiglio, Paula InésGarcía Vaquero, IreneGómez Rosas, IreneGoñi, MarinaVillamar, ManuelaMorín, MatíasMoreno Pelayo, Miguel A.Elgoyhen, Ana BelenDel Castillo, Francisco J.Dalamon, Viviana KarinaDel Castillo, IgnacioNON-SYNDROMIC HEARING IMPAIRMENTDFNB16STRCSTEREOCILINhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.Keywords: non-syndromic hearing impairment; DFNB16; STRC; stereocilin; genetic epidemiologyFil: Domínguez Ruiz, María. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; EspañaFil: Ruiz Palmero, Laura. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; EspañaFil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: García Vaquero, Irene. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; EspañaFil: Gómez Rosas, Irene. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; EspañaFil: Goñi, Marina. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; EspañaFil: Villamar, Manuela. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; EspañaFil: Morín, Matías. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; EspañaFil: Moreno Pelayo, Miguel A.. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; EspañaFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; ArgentinaFil: Del Castillo, Francisco J.. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; EspañaFil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Del Castillo, Ignacio. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; EspañaMultidisciplinary Digital Publishing Institute2023-10-31info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/232752Domínguez Ruiz, María; Ruiz Palmero, Laura; Buonfiglio, Paula Inés; García Vaquero, Irene; Gómez Rosas, Irene; et al.; Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects; Multidisciplinary Digital Publishing Institute; Biomedicines; 11; 11; 31-10-2023; 1-102227-9059CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines11112943info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2227-9059/11/11/2943info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:22Zoai:ri.conicet.gov.ar:11336/232752instacron: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:34982025-09-29 09:46:22.73CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
title Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
spellingShingle Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
Domínguez Ruiz, María
NON-SYNDROMIC HEARING IMPAIRMENT
DFNB16
STRC
STEREOCILIN
title_short Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
title_full Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
title_fullStr Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
title_full_unstemmed Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
title_sort Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects
dc.creator.none.fl_str_mv Domínguez Ruiz, María
Ruiz Palmero, Laura
Buonfiglio, Paula Inés
García Vaquero, Irene
Gómez Rosas, Irene
Goñi, Marina
Villamar, Manuela
Morín, Matías
Moreno Pelayo, Miguel A.
Elgoyhen, Ana Belen
Del Castillo, Francisco J.
Dalamon, Viviana Karina
Del Castillo, Ignacio
author Domínguez Ruiz, María
author_facet Domínguez Ruiz, María
Ruiz Palmero, Laura
Buonfiglio, Paula Inés
García Vaquero, Irene
Gómez Rosas, Irene
Goñi, Marina
Villamar, Manuela
Morín, Matías
Moreno Pelayo, Miguel A.
Elgoyhen, Ana Belen
Del Castillo, Francisco J.
Dalamon, Viviana Karina
Del Castillo, Ignacio
author_role author
author2 Ruiz Palmero, Laura
Buonfiglio, Paula Inés
García Vaquero, Irene
Gómez Rosas, Irene
Goñi, Marina
Villamar, Manuela
Morín, Matías
Moreno Pelayo, Miguel A.
Elgoyhen, Ana Belen
Del Castillo, Francisco J.
Dalamon, Viviana Karina
Del Castillo, Ignacio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NON-SYNDROMIC HEARING IMPAIRMENT
DFNB16
STRC
STEREOCILIN
topic NON-SYNDROMIC HEARING IMPAIRMENT
DFNB16
STRC
STEREOCILIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.Keywords: non-syndromic hearing impairment; DFNB16; STRC; stereocilin; genetic epidemiology
Fil: Domínguez Ruiz, María. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Ruiz Palmero, Laura. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: García Vaquero, Irene. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Gómez Rosas, Irene. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Goñi, Marina. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España
Fil: Villamar, Manuela. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Morín, Matías. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Moreno Pelayo, Miguel A.. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Farmacología; Argentina
Fil: Del Castillo, Francisco J.. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
Fil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Del Castillo, Ignacio. Comunidad de Madrid. Hospital Universitario Ramón y Cajal. Servicio de Genética.; España. Ministerio de Ciencias, Innovación y Universidades. Centro de Investigación Biomédica en Red Enfermedades Raras.; España
description Non-syndromic hearing impairment (NSHI) is a very heterogeneous genetic condition, involving over 130 genes. Mutations in GJB2, encoding connexin-26, are a major cause of NSHI (the DFNB1 type), but few other genes have significant epidemiological contributions. Mutations in the STRC gene result in the DFNB16 type of autosomal recessive NSHI, a common cause of moderate hearing loss. STRC is located in a tandem duplicated region that includes the STRCP1 pseudogene, and so it is prone to rearrangements causing structural variations. Firstly, we screened a cohort of 122 Spanish familial cases of non-DFNB1 NSHI with at least two affected siblings and unaffected parents, and with different degrees of hearing loss (mild to profound). Secondly, we screened a cohort of 64 Spanish sporadic non-DFNB1 cases, and a cohort of 35 Argentinean non-DFNB1 cases, all of them with moderate hearing loss. Amplification of marker D15S784, massively parallel DNA sequencing, multiplex ligation-dependent probe amplification and long-range gene-specific PCR followed by Sanger sequencing were used to search and confirm single-nucleotide variants (SNVs) and deletions involving STRC. Causative variants were found in 13 Spanish familial cases (10.7%), 5 Spanish simplex cases (7.8%) and 2 Argentinean cases (5.7%). In all, 34 deleted alleles and 6 SNVs, 5 of which are novel. All affected subjects had moderate hearing impairment. Our results further support this strong genotype–phenotype correlation and highlight the significant contribution of STRC mutations to moderate NSHI in the Spanish population.Keywords: non-syndromic hearing impairment; DFNB16; STRC; stereocilin; genetic epidemiology
publishDate 2023
dc.date.none.fl_str_mv 2023-10-31
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/11336/232752
Domínguez Ruiz, María; Ruiz Palmero, Laura; Buonfiglio, Paula Inés; García Vaquero, Irene; Gómez Rosas, Irene; et al.; Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects; Multidisciplinary Digital Publishing Institute; Biomedicines; 11; 11; 31-10-2023; 1-10
2227-9059
CONICET Digital
CONICET
url http://hdl.handle.net/11336/232752
identifier_str_mv Domínguez Ruiz, María; Ruiz Palmero, Laura; Buonfiglio, Paula Inés; García Vaquero, Irene; Gómez Rosas, Irene; et al.; Novel Pathogenic Variants in the Gene Encoding Stereocilin (STRC) Causing Non-Syndromic Moderate Hearing Loss in Spanish and Argentinean Subjects; Multidisciplinary Digital Publishing Institute; Biomedicines; 11; 11; 31-10-2023; 1-10
2227-9059
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/biomedicines11112943
info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2227-9059/11/11/2943
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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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