A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis

Autores
Targovnik, Héctor M.; Barh, Debmalya; Papendieck, Patricia; Adrover, Ezequiela; Gallo, Ariel M.; Chiesa, Ana; Marques Da Silva, Wanderson; Azevedo, Vasco; Rivolta, Carina M.
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
DICER1 syndrome is an autosomal-dominant disorder that results in malignant or benign tumors. A number of distinct pathogenic germline and somatic variants have been identified as causing multinodular goiter (MNG). The purpose of the present study was to identify and characterize the genetic cause underlying the familial form of MNG through a whole-exome sequencing (WES) analysis in an Argentine family with three affected siblings. Clinical, biochemical and molecular genetics as well as bioinformatics analysis were performed. A novel heterozygous variant in the DICER1 gene was identified in the proband patient by WES. The variant was a single guanine deletion at nucleotide position 2,042 (NM_177438.3:c.2042del) resulting in a frameshift at amino acid 681 with a putative premature stop codon [NP_803187.1:p.Gly681ValfsTer4]. Family segregation analysis showed that his affected sister and his affected brother also were heterozygous for same variant, whereas the father was a healthy heterozygous carrier of the variant and the healthy mother harbor only wild-type alleles in the DICER1 gene. We have also observed that the frameshift variant does not interfere with the pre-mRNA splicing of the exon 13. In addition, two clinically relevant heterozygous variants, not associated with thyroid disease, were also identified in index sibling using the Franklin platform, a frameshift [NP_000234.1:p.Thr55AsnfsTer49] in the MEFV gene (familial mediterranean fever) and a missense [NP_004530.1:p.Ala422Thr] in the NARS1 gene (neurodevelopmental delay and ataxia). In conclusion, in the present study we have identified a novel frameshift variant corresponding to NP_803187.1:p.Gly681ValfsTer4 in the DUF 283 domain of DICER1. The results were in accordance with previous observations confirming the genetic heterogeneity of DICER1 syndrome. Moreover, the identification of this variant in the unaffected father substantiates the hypothesis of incomplete/reduced penetrance.
Instituto de Biotecnología
Fil: Targovnik, Héctor M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Barh, Debmalya. Federal University of Minas Gerais. Department of Genetics, Ecology & Evolution. Institute of Biological Sciences; Brasil
Fil: Barh, Debmalya. Institute of Integrative Omics & Applied Biotechnology; India
Fil: Papendieck, Patricia. Hospital de Niños “Ricardo Gutiérrez”. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Papendieck, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. División Endocrinología. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Adrover, Ezequiela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Adrover, Ezequiela. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Gallo, Ariel M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Gallo, Ariel M. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Gallo, Ariel M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Chiesa, Ana. Hospital de Niños “Ricardo Gutiérrez”. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Chiesa, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. División Endocrinología. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Marques Da Silva, Wanderson. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Azevedo, Vasco. Federal University of Minas Gerais. Department of Genetics, Ecology & Evolution. Institute of Biological Sciences; Brasil
Fil: Rivolta, Carina M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Rivolta, Carina M. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Rivolta, Carina M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fuente
Endocrine 87 (3) : 1150-1161. (March 2025)
Materia
Bocio
Genética
Análisis de Secuencias
Bioinformática
Goitre
Genetics
Sequence Analysis
Bioinformatics
Nivel de accesibilidad
acceso restringido
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/21729
Acceder
id INTADig_998ccf4f9b89875769d0b31561778ed0
oai_identifier_str oai:localhost:20.500.12123/21729
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysisTargovnik, Héctor M.Barh, DebmalyaPapendieck, PatriciaAdrover, EzequielaGallo, Ariel M.Chiesa, AnaMarques Da Silva, WandersonAzevedo, VascoRivolta, Carina M.BocioGenéticaAnálisis de SecuenciasBioinformáticaGoitreGeneticsSequence AnalysisBioinformaticsDICER1 syndrome is an autosomal-dominant disorder that results in malignant or benign tumors. A number of distinct pathogenic germline and somatic variants have been identified as causing multinodular goiter (MNG). The purpose of the present study was to identify and characterize the genetic cause underlying the familial form of MNG through a whole-exome sequencing (WES) analysis in an Argentine family with three affected siblings. Clinical, biochemical and molecular genetics as well as bioinformatics analysis were performed. A novel heterozygous variant in the DICER1 gene was identified in the proband patient by WES. The variant was a single guanine deletion at nucleotide position 2,042 (NM_177438.3:c.2042del) resulting in a frameshift at amino acid 681 with a putative premature stop codon [NP_803187.1:p.Gly681ValfsTer4]. Family segregation analysis showed that his affected sister and his affected brother also were heterozygous for same variant, whereas the father was a healthy heterozygous carrier of the variant and the healthy mother harbor only wild-type alleles in the DICER1 gene. We have also observed that the frameshift variant does not interfere with the pre-mRNA splicing of the exon 13. In addition, two clinically relevant heterozygous variants, not associated with thyroid disease, were also identified in index sibling using the Franklin platform, a frameshift [NP_000234.1:p.Thr55AsnfsTer49] in the MEFV gene (familial mediterranean fever) and a missense [NP_004530.1:p.Ala422Thr] in the NARS1 gene (neurodevelopmental delay and ataxia). In conclusion, in the present study we have identified a novel frameshift variant corresponding to NP_803187.1:p.Gly681ValfsTer4 in the DUF 283 domain of DICER1. The results were in accordance with previous observations confirming the genetic heterogeneity of DICER1 syndrome. Moreover, the identification of this variant in the unaffected father substantiates the hypothesis of incomplete/reduced penetrance.Instituto de BiotecnologíaFil: Targovnik, Héctor M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; ArgentinaFil: Barh, Debmalya. Federal University of Minas Gerais. Department of Genetics, Ecology & Evolution. Institute of Biological Sciences; BrasilFil: Barh, Debmalya. Institute of Integrative Omics & Applied Biotechnology; IndiaFil: Papendieck, Patricia. Hospital de Niños “Ricardo Gutiérrez”. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Papendieck, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. División Endocrinología. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Adrover, Ezequiela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; ArgentinaFil: Adrover, Ezequiela. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); ArgentinaFil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); ArgentinaFil: Gallo, Ariel M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; ArgentinaFil: Gallo, Ariel M. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); ArgentinaFil: Gallo, Ariel M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); ArgentinaFil: Chiesa, Ana. Hospital de Niños “Ricardo Gutiérrez”. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Chiesa, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. División Endocrinología. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Marques Da Silva, Wanderson. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Azevedo, Vasco. Federal University of Minas Gerais. Department of Genetics, Ecology & Evolution. Institute of Biological Sciences; BrasilFil: Rivolta, Carina M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; ArgentinaFil: Rivolta, Carina M. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); ArgentinaFil: Rivolta, Carina M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); ArgentinaSpringer2025-03-19T13:11:09Z2025-03-19T13:11:09Z2025-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/21729https://link.springer.com/article/10.1007/s12020-024-04098-31559-0100https://doi.org/10.1007/s12020-024-04098-3Endocrine 87 (3) : 1150-1161. (March 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/restrictedAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-29T13:47:12Zoai:localhost:20.500.12123/21729instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-29 13:47:13.066INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
title A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
spellingShingle A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
Targovnik, Héctor M.
Bocio
Genética
Análisis de Secuencias
Bioinformática
Goitre
Genetics
Sequence Analysis
Bioinformatics
title_short A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
title_full A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
title_fullStr A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
title_full_unstemmed A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
title_sort A novel pathogenic DICER1 gene variant is associated with hereditary multinodular goiter in an Argentine family as evidenced by clinical, biochemical and molecular genetic analysis
dc.creator.none.fl_str_mv Targovnik, Héctor M.
Barh, Debmalya
Papendieck, Patricia
Adrover, Ezequiela
Gallo, Ariel M.
Chiesa, Ana
Marques Da Silva, Wanderson
Azevedo, Vasco
Rivolta, Carina M.
author Targovnik, Héctor M.
author_facet Targovnik, Héctor M.
Barh, Debmalya
Papendieck, Patricia
Adrover, Ezequiela
Gallo, Ariel M.
Chiesa, Ana
Marques Da Silva, Wanderson
Azevedo, Vasco
Rivolta, Carina M.
author_role author
author2 Barh, Debmalya
Papendieck, Patricia
Adrover, Ezequiela
Gallo, Ariel M.
Chiesa, Ana
Marques Da Silva, Wanderson
Azevedo, Vasco
Rivolta, Carina M.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Bocio
Genética
Análisis de Secuencias
Bioinformática
Goitre
Genetics
Sequence Analysis
Bioinformatics
topic Bocio
Genética
Análisis de Secuencias
Bioinformática
Goitre
Genetics
Sequence Analysis
Bioinformatics
dc.description.none.fl_txt_mv DICER1 syndrome is an autosomal-dominant disorder that results in malignant or benign tumors. A number of distinct pathogenic germline and somatic variants have been identified as causing multinodular goiter (MNG). The purpose of the present study was to identify and characterize the genetic cause underlying the familial form of MNG through a whole-exome sequencing (WES) analysis in an Argentine family with three affected siblings. Clinical, biochemical and molecular genetics as well as bioinformatics analysis were performed. A novel heterozygous variant in the DICER1 gene was identified in the proband patient by WES. The variant was a single guanine deletion at nucleotide position 2,042 (NM_177438.3:c.2042del) resulting in a frameshift at amino acid 681 with a putative premature stop codon [NP_803187.1:p.Gly681ValfsTer4]. Family segregation analysis showed that his affected sister and his affected brother also were heterozygous for same variant, whereas the father was a healthy heterozygous carrier of the variant and the healthy mother harbor only wild-type alleles in the DICER1 gene. We have also observed that the frameshift variant does not interfere with the pre-mRNA splicing of the exon 13. In addition, two clinically relevant heterozygous variants, not associated with thyroid disease, were also identified in index sibling using the Franklin platform, a frameshift [NP_000234.1:p.Thr55AsnfsTer49] in the MEFV gene (familial mediterranean fever) and a missense [NP_004530.1:p.Ala422Thr] in the NARS1 gene (neurodevelopmental delay and ataxia). In conclusion, in the present study we have identified a novel frameshift variant corresponding to NP_803187.1:p.Gly681ValfsTer4 in the DUF 283 domain of DICER1. The results were in accordance with previous observations confirming the genetic heterogeneity of DICER1 syndrome. Moreover, the identification of this variant in the unaffected father substantiates the hypothesis of incomplete/reduced penetrance.
Instituto de Biotecnología
Fil: Targovnik, Héctor M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Barh, Debmalya. Federal University of Minas Gerais. Department of Genetics, Ecology & Evolution. Institute of Biological Sciences; Brasil
Fil: Barh, Debmalya. Institute of Integrative Omics & Applied Biotechnology; India
Fil: Papendieck, Patricia. Hospital de Niños “Ricardo Gutiérrez”. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Papendieck, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. División Endocrinología. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Adrover, Ezequiela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Adrover, Ezequiela. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Adrover, Ezequiela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Gallo, Ariel M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Gallo, Ariel M. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Gallo, Ariel M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Chiesa, Ana. Hospital de Niños “Ricardo Gutiérrez”. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Chiesa, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. División Endocrinología. Centro de Investigaciones Endocrinológicas; Argentina
Fil: Marques Da Silva, Wanderson. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; Argentina
Fil: Marques Da Silva, Wanderson. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Azevedo, Vasco. Federal University of Minas Gerais. Department of Genetics, Ecology & Evolution. Institute of Biological Sciences; Brasil
Fil: Rivolta, Carina M. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología, Biotecnología y Genética. Cátedra de Genética; Argentina
Fil: Rivolta, Carina M. Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
Fil: Rivolta, Carina M. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Inmunología, Genética y Metabolismo (INIGEM); Argentina
description DICER1 syndrome is an autosomal-dominant disorder that results in malignant or benign tumors. A number of distinct pathogenic germline and somatic variants have been identified as causing multinodular goiter (MNG). The purpose of the present study was to identify and characterize the genetic cause underlying the familial form of MNG through a whole-exome sequencing (WES) analysis in an Argentine family with three affected siblings. Clinical, biochemical and molecular genetics as well as bioinformatics analysis were performed. A novel heterozygous variant in the DICER1 gene was identified in the proband patient by WES. The variant was a single guanine deletion at nucleotide position 2,042 (NM_177438.3:c.2042del) resulting in a frameshift at amino acid 681 with a putative premature stop codon [NP_803187.1:p.Gly681ValfsTer4]. Family segregation analysis showed that his affected sister and his affected brother also were heterozygous for same variant, whereas the father was a healthy heterozygous carrier of the variant and the healthy mother harbor only wild-type alleles in the DICER1 gene. We have also observed that the frameshift variant does not interfere with the pre-mRNA splicing of the exon 13. In addition, two clinically relevant heterozygous variants, not associated with thyroid disease, were also identified in index sibling using the Franklin platform, a frameshift [NP_000234.1:p.Thr55AsnfsTer49] in the MEFV gene (familial mediterranean fever) and a missense [NP_004530.1:p.Ala422Thr] in the NARS1 gene (neurodevelopmental delay and ataxia). In conclusion, in the present study we have identified a novel frameshift variant corresponding to NP_803187.1:p.Gly681ValfsTer4 in the DUF 283 domain of DICER1. The results were in accordance with previous observations confirming the genetic heterogeneity of DICER1 syndrome. Moreover, the identification of this variant in the unaffected father substantiates the hypothesis of incomplete/reduced penetrance.
publishDate 2025
dc.date.none.fl_str_mv 2025-03-19T13:11:09Z
2025-03-19T13:11:09Z
2025-03
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/20.500.12123/21729
https://link.springer.com/article/10.1007/s12020-024-04098-3
1559-0100
https://doi.org/10.1007/s12020-024-04098-3
url http://hdl.handle.net/20.500.12123/21729
https://link.springer.com/article/10.1007/s12020-024-04098-3
https://doi.org/10.1007/s12020-024-04098-3
identifier_str_mv 1559-0100
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/restrictedAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv restrictedAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Endocrine 87 (3) : 1150-1161. (March 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
_version_ 1844619202019721216
score 12.559606

Publicaciones similares