Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism
- Autores
- Siffo, Sofía; Adrover, Ezequiela; Citterio, Cintia Eliana; Miras, Mirta Beatriz; Balbi, Viviana A.; Chiesa, Ana Elena; Weill, Jacques; Sobrero, Gabriela; González, Verónica G.; Papendieck, Patricia; Bueno Martinez, Elena; González Sarmiento, Rogelio; Rivolta, Carina Marcela; Targovnik, Hector Manuel
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain.
Fil: Siffo, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Citterio, Cintia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Miras, Mirta Beatriz. Provincia de Córdoba. Hospital de Niños Santísima Trinidad. Servicio de Endocrinología; Argentina
Fil: Balbi, Viviana A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina
Fil: Weill, Jacques. Universitaire de Lille. Centre Hospitalier Regional; Francia
Fil: Sobrero, Gabriela. Provincia de Córdoba. Hospital de Niños Santísima Trinidad. Servicio de Endocrinología; Argentina
Fil: González, Verónica G.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina
Fil: Papendieck, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina
Fil: Bueno Martinez, Elena. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; España
Fil: González Sarmiento, Rogelio. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; España
Fil: Rivolta, Carina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina - Materia
-
Thyroglobulin gene
Hypothyroidism
Goiter
Mutation
Truncated thyroglobulin protein - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/51491
Ver los metadatos del registro completo
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Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidismSiffo, SofíaAdrover, EzequielaCitterio, Cintia ElianaMiras, Mirta BeatrizBalbi, Viviana A.Chiesa, Ana ElenaWeill, JacquesSobrero, GabrielaGonzález, Verónica G.Papendieck, PatriciaBueno Martinez, ElenaGonzález Sarmiento, RogelioRivolta, Carina MarcelaTargovnik, Hector ManuelThyroglobulin geneHypothyroidismGoiterMutationTruncated thyroglobulin proteinhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain.Fil: Siffo, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Citterio, Cintia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Miras, Mirta Beatriz. Provincia de Córdoba. Hospital de Niños Santísima Trinidad. Servicio de Endocrinología; ArgentinaFil: Balbi, Viviana A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Weill, Jacques. Universitaire de Lille. Centre Hospitalier Regional; FranciaFil: Sobrero, Gabriela. Provincia de Córdoba. Hospital de Niños Santísima Trinidad. Servicio de Endocrinología; ArgentinaFil: González, Verónica G.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Papendieck, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; ArgentinaFil: Bueno Martinez, Elena. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; EspañaFil: González Sarmiento, Rogelio. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; EspañaFil: Rivolta, Carina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaElsevier Ireland2017-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/51491Siffo, Sofía; Adrover, Ezequiela; Citterio, Cintia Eliana; Miras, Mirta Beatriz; Balbi, Viviana A.; et al.; Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism; Elsevier Ireland; Molecular and Cellular Endocrinology; 30; 12-2017; 1-160303-72071872-8057CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0303720717306378info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2017.12.009info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:59:49Zoai:ri.conicet.gov.ar:11336/51491instacron: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 09:59:49.981CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| title |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| spellingShingle |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism Siffo, Sofía Thyroglobulin gene Hypothyroidism Goiter Mutation Truncated thyroglobulin protein |
| title_short |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| title_full |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| title_fullStr |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| title_full_unstemmed |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| title_sort |
Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism |
| dc.creator.none.fl_str_mv |
Siffo, Sofía Adrover, Ezequiela Citterio, Cintia Eliana Miras, Mirta Beatriz Balbi, Viviana A. Chiesa, Ana Elena Weill, Jacques Sobrero, Gabriela González, Verónica G. Papendieck, Patricia Bueno Martinez, Elena González Sarmiento, Rogelio Rivolta, Carina Marcela Targovnik, Hector Manuel |
| author |
Siffo, Sofía |
| author_facet |
Siffo, Sofía Adrover, Ezequiela Citterio, Cintia Eliana Miras, Mirta Beatriz Balbi, Viviana A. Chiesa, Ana Elena Weill, Jacques Sobrero, Gabriela González, Verónica G. Papendieck, Patricia Bueno Martinez, Elena González Sarmiento, Rogelio Rivolta, Carina Marcela Targovnik, Hector Manuel |
| author_role |
author |
| author2 |
Adrover, Ezequiela Citterio, Cintia Eliana Miras, Mirta Beatriz Balbi, Viviana A. Chiesa, Ana Elena Weill, Jacques Sobrero, Gabriela González, Verónica G. Papendieck, Patricia Bueno Martinez, Elena González Sarmiento, Rogelio Rivolta, Carina Marcela Targovnik, Hector Manuel |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Thyroglobulin gene Hypothyroidism Goiter Mutation Truncated thyroglobulin protein |
| topic |
Thyroglobulin gene Hypothyroidism Goiter Mutation Truncated thyroglobulin protein |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain. Fil: Siffo, Sofía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Citterio, Cintia Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Miras, Mirta Beatriz. Provincia de Córdoba. Hospital de Niños Santísima Trinidad. Servicio de Endocrinología; Argentina Fil: Balbi, Viviana A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina Fil: Chiesa, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Weill, Jacques. Universitaire de Lille. Centre Hospitalier Regional; Francia Fil: Sobrero, Gabriela. Provincia de Córdoba. Hospital de Niños Santísima Trinidad. Servicio de Endocrinología; Argentina Fil: González, Verónica G.. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; Argentina Fil: Papendieck, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas ; Argentina Fil: Bueno Martinez, Elena. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; España Fil: González Sarmiento, Rogelio. Universidad de Salamanca; España. Consejo Superior de Investigaciones Científicas; España Fil: Rivolta, Carina Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Targovnik, Hector Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina |
| description |
Thyroid dyshormonogenesis due to thyroglobulin (TG) gene mutations have an estimated incidence of approximately 1 in 100,000 newborns. The clinical spectrum ranges from euthyroid to mild or severe hypothyroidism. Up to now, one hundred seventeen deleterious mutations in the TG gene have been identified and characterized. The purpose of the present study was to identify and characterize new mutations in the TG gene. We report eight patients from seven unrelated families with goiter, hypothyroidism and low levels of serum TG. All patients underwent clinical, biochemical and image evaluation. Sequencing of DNA, genotyping, as well as bioinformatics analysis were performed. Molecular analyses revealed three novel inactivating TG mutations: c.5560G>T [p.E1835*], c.7084G>C [p.A2343P] and c.7093T>C [p.W2346R], and four previously reported mutations: c.378C>A [p.Y107*], c.886C>T [p.R277*], c.1351C>T [p.R432*] and c.7007G>A [p.R2317Q]. Two patients carried homozygous mutations (p.R277*/p.R277*, p.W2346R/p.W2346R), four were compound heterozygous mutations (p.Y107*/p.R277* (two unrelated patients), p.R432*/p.A2343P, p.Y107*/p.R2317Q) and two siblings from another family had a single p.E1835* mutated allele. Additionally, we include the analysis of 48 patients from 31 unrelated families with TG mutations identified in our present and previous studies. Our observation shows that mutations in both TG alleles were found in 27 families (9 as homozygote and 18 as heterozygote compound), whereas in the remaining four families only one mutated allele was detected. The majority of the detected mutations occur in exons 4, 7, 38 and 40. 28 different mutations were identified, 33 of the 96 TG alleles encoded the change p.R277*. In conclusion, our results confirm the genetic heterogeneity of TG defects and the pathophysiological importance of the predicted TG misfolding and therefore thyroid hormone formation as a consequence of truncated TG proteins and/or missense mutations located within its ACHE-like domain. |
| publishDate |
2017 |
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2017-12 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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http://hdl.handle.net/11336/51491 Siffo, Sofía; Adrover, Ezequiela; Citterio, Cintia Eliana; Miras, Mirta Beatriz; Balbi, Viviana A.; et al.; Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism; Elsevier Ireland; Molecular and Cellular Endocrinology; 30; 12-2017; 1-16 0303-7207 1872-8057 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/51491 |
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Siffo, Sofía; Adrover, Ezequiela; Citterio, Cintia Eliana; Miras, Mirta Beatriz; Balbi, Viviana A.; et al.; Molecular analysis of thyroglobulin mutations found in patients with goiter and hypothyroidism; Elsevier Ireland; Molecular and Cellular Endocrinology; 30; 12-2017; 1-16 0303-7207 1872-8057 CONICET Digital CONICET |
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eng |
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eng |
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Elsevier Ireland |
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Elsevier Ireland |
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