Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome

Autores
Buonfiglio, Paula Inés; Izquierdo, Agustin; Pace, Mariela Vanina; Grinberg, Sofía Eliana; Lotersztein, Vanesa; Brun, Paloma Laura; Bruque, Carlos David; Elgoyhen, Ana Belen; Dalamon, Viviana Karina
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling.
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: Izquierdo, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Pace, Mariela Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Grinberg, Sofía Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lotersztein, Vanesa. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Brun, Paloma Laura. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Bruque, Carlos David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Elgoyhen, Ana Belen. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología. 3º Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
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
Materia
WAARDENBURG SYNDROME
WES
HEARING LOSS
CNV
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:11336/248223
Acceder
id CONICETDig_51b85a18cc7c80678086bb6c385d393c
oai_identifier_str oai:ri.conicet.gov.ar:11336/248223
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg SyndromeBuonfiglio, Paula InésIzquierdo, AgustinPace, Mariela VaninaGrinberg, Sofía ElianaLotersztein, VanesaBrun, Paloma LauraBruque, Carlos DavidElgoyhen, Ana BelenDalamon, Viviana KarinaWAARDENBURG SYNDROMEWESHEARING LOSSCNVhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling.Fil: Buonfiglio, Paula Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Izquierdo, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Pace, Mariela Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Grinberg, Sofía Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lotersztein, Vanesa. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Brun, Paloma Laura. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Bruque, Carlos David. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Elgoyhen, Ana Belen. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología. 3º Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Dalamon, Viviana Karina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaMDPI2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/248223Buonfiglio, Paula Inés; Izquierdo, Agustin; Pace, Mariela Vanina; Grinberg, Sofía Eliana; Lotersztein, Vanesa; et al.; Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome; MDPI; Journal of Personalized Medicine; 14; 9; 8-2024; 1-132075-4426CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2075-4426/14/9/906info:eu-repo/semantics/altIdentifier/doi/10.3390/jpm14090906info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:23Zoai:ri.conicet.gov.ar:11336/248223instacron: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 10:08:23.383CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
title Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
spellingShingle Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
Buonfiglio, Paula Inés
WAARDENBURG SYNDROME
WES
HEARING LOSS
CNV
title_short Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
title_full Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
title_fullStr Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
title_full_unstemmed Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
title_sort Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome
dc.creator.none.fl_str_mv Buonfiglio, Paula Inés
Izquierdo, Agustin
Pace, Mariela Vanina
Grinberg, Sofía Eliana
Lotersztein, Vanesa
Brun, Paloma Laura
Bruque, Carlos David
Elgoyhen, Ana Belen
Dalamon, Viviana Karina
author Buonfiglio, Paula Inés
author_facet Buonfiglio, Paula Inés
Izquierdo, Agustin
Pace, Mariela Vanina
Grinberg, Sofía Eliana
Lotersztein, Vanesa
Brun, Paloma Laura
Bruque, Carlos David
Elgoyhen, Ana Belen
Dalamon, Viviana Karina
author_role author
author2 Izquierdo, Agustin
Pace, Mariela Vanina
Grinberg, Sofía Eliana
Lotersztein, Vanesa
Brun, Paloma Laura
Bruque, Carlos David
Elgoyhen, Ana Belen
Dalamon, Viviana Karina
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv WAARDENBURG SYNDROME
WES
HEARING LOSS
CNV
topic WAARDENBURG SYNDROME
WES
HEARING LOSS
CNV
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling.
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: Izquierdo, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina
Fil: Pace, Mariela Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Grinberg, Sofía Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Lotersztein, Vanesa. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; Argentina
Fil: Brun, Paloma Laura. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; Argentina
Fil: Bruque, Carlos David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Elgoyhen, Ana Belen. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología. 3º Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
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
description Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
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/11336/248223
Buonfiglio, Paula Inés; Izquierdo, Agustin; Pace, Mariela Vanina; Grinberg, Sofía Eliana; Lotersztein, Vanesa; et al.; Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome; MDPI; Journal of Personalized Medicine; 14; 9; 8-2024; 1-13
2075-4426
CONICET Digital
CONICET
url http://hdl.handle.net/11336/248223
identifier_str_mv Buonfiglio, Paula Inés; Izquierdo, Agustin; Pace, Mariela Vanina; Grinberg, Sofía Eliana; Lotersztein, Vanesa; et al.; Comprehensive Approach for the Genetic Diagnosis of Patients with Waardenburg Syndrome; MDPI; Journal of Personalized Medicine; 14; 9; 8-2024; 1-13
2075-4426
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2075-4426/14/9/906
info:eu-repo/semantics/altIdentifier/doi/10.3390/jpm14090906
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
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 MDPI
publisher.none.fl_str_mv MDPI
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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