Gray platelet syndrome: Novel mutations of the NBEAL2 gene
- Autores
- Bottega, Roberta; Nicchia, Elena; Alfano, Caterina; Glembotsky, Ana Claudia; Pastore, Annalisa; Bertaggia Calderara, Debora; Bisig, Bettina; Duchosal, Michel A.; Arbesú, Guillermo; Alberio, Lorenzo; Heller, Paula Graciela; Savoia, Anna
- Año de publicación
- 2017
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Gray platelet syndrome (GPS) is a rare inherited macrothrombocytopenia characterized by reduction of a-granules in platelets and megakaryocytes associated with mild-tomoderate bleeding and myelofibrosis [1]. As reported in at least 28 unrelated families [1], GPS is caused by mutations of NBEAL2, the gene encoding for the neurobeachin-like-2 protein. NBEAL2 is a member of the family containing the BEACH (BEige And Chediak Higashi) domain, a conserved region involved in vesicular trafficking that may be critical for the a-granule development [2]. Here, we report novel mutations of NBEAL2 in two affected individuals (P1 and P2), who were previously diagnosed with immune thrombocytopenia (ITP) and then suspected to have GPS because of absence of azurophilic granules on May-Grunwald-Giemsa staining. In P1, sequencing analysis identified an € homozygous missense variant (c.6212G > C; p.Arg2071Pro; Supporting Information Fig. S1). Since her parents were not available for the segregation analysis, we hypothesised that the two mutant alleles were identical by descent because of homozygosity of all the polymorphic markers at the NBEAL2 locus (data not shown). Moreover, the potential hemizygous condition was excluded using statistical analyses of NBEAL2 amplicon coverage as previously reported (Supporting Information Fig. S1C) [3]. In P2, we detected one maternal nonsense (c.3839C > T; p.Arg1280*) and one paternal missense (c.6477C > G; p.His2159Gln; Supporting Information Fig. S1). The three NBEAL2 variants are reported in SNPs databases but with a minor allele frequency <0.01%.
Fil: Bottega, Roberta. Università degli Studi di Trieste; Italia
Fil: Nicchia, Elena. Università degli Studi di Trieste; Italia
Fil: Alfano, Caterina. King's College London; Reino Unido
Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Pastore, Annalisa. King's College London; Reino Unido
Fil: Bertaggia Calderara, Debora. Universite de Lausanne; Suiza
Fil: Bisig, Bettina. Universite de Lausanne; Suiza
Fil: Duchosal, Michel A.. Universite de Lausanne; Suiza
Fil: Arbesú, Guillermo. Hospital Pediátrico Dr. Humberto Notti; Argentina
Fil: Alberio, Lorenzo. Universite de Lausanne; Suiza
Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Institute for Maternal and Child Health; Italia - Materia
-
Nbeal2
Gray Platelet Syndrome
Platelets
Mutations - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/47272
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Gray platelet syndrome: Novel mutations of the NBEAL2 geneBottega, RobertaNicchia, ElenaAlfano, CaterinaGlembotsky, Ana ClaudiaPastore, AnnalisaBertaggia Calderara, DeboraBisig, BettinaDuchosal, Michel A.Arbesú, GuillermoAlberio, LorenzoHeller, Paula GracielaSavoia, AnnaNbeal2Gray Platelet SyndromePlateletsMutationshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Gray platelet syndrome (GPS) is a rare inherited macrothrombocytopenia characterized by reduction of a-granules in platelets and megakaryocytes associated with mild-tomoderate bleeding and myelofibrosis [1]. As reported in at least 28 unrelated families [1], GPS is caused by mutations of NBEAL2, the gene encoding for the neurobeachin-like-2 protein. NBEAL2 is a member of the family containing the BEACH (BEige And Chediak Higashi) domain, a conserved region involved in vesicular trafficking that may be critical for the a-granule development [2]. Here, we report novel mutations of NBEAL2 in two affected individuals (P1 and P2), who were previously diagnosed with immune thrombocytopenia (ITP) and then suspected to have GPS because of absence of azurophilic granules on May-Grunwald-Giemsa staining. In P1, sequencing analysis identified an € homozygous missense variant (c.6212G > C; p.Arg2071Pro; Supporting Information Fig. S1). Since her parents were not available for the segregation analysis, we hypothesised that the two mutant alleles were identical by descent because of homozygosity of all the polymorphic markers at the NBEAL2 locus (data not shown). Moreover, the potential hemizygous condition was excluded using statistical analyses of NBEAL2 amplicon coverage as previously reported (Supporting Information Fig. S1C) [3]. In P2, we detected one maternal nonsense (c.3839C > T; p.Arg1280*) and one paternal missense (c.6477C > G; p.His2159Gln; Supporting Information Fig. S1). The three NBEAL2 variants are reported in SNPs databases but with a minor allele frequency <0.01%.Fil: Bottega, Roberta. Università degli Studi di Trieste; ItaliaFil: Nicchia, Elena. Università degli Studi di Trieste; ItaliaFil: Alfano, Caterina. King's College London; Reino UnidoFil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pastore, Annalisa. King's College London; Reino UnidoFil: Bertaggia Calderara, Debora. Universite de Lausanne; SuizaFil: Bisig, Bettina. Universite de Lausanne; SuizaFil: Duchosal, Michel A.. Universite de Lausanne; SuizaFil: Arbesú, Guillermo. Hospital Pediátrico Dr. Humberto Notti; ArgentinaFil: Alberio, Lorenzo. Universite de Lausanne; SuizaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Savoia, Anna. Università degli Studi di Trieste; Italia. Institute for Maternal and Child Health; ItaliaWiley-liss, Div John Wiley & Sons Inc2017-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/47272Bottega, Roberta; Nicchia, Elena; Alfano, Caterina; Glembotsky, Ana Claudia; Pastore, Annalisa; et al.; Gray platelet syndrome: Novel mutations of the NBEAL2 gene; Wiley-liss, Div John Wiley & Sons Inc; American Journal Of Hematology; 92; 2; 2-2017; E20-E220361-8609CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/ajh.24610info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.24610info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:37Zoai:ri.conicet.gov.ar:11336/47272instacron: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 09:51:37.828CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
title |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
spellingShingle |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene Bottega, Roberta Nbeal2 Gray Platelet Syndrome Platelets Mutations |
title_short |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
title_full |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
title_fullStr |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
title_full_unstemmed |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
title_sort |
Gray platelet syndrome: Novel mutations of the NBEAL2 gene |
dc.creator.none.fl_str_mv |
Bottega, Roberta Nicchia, Elena Alfano, Caterina Glembotsky, Ana Claudia Pastore, Annalisa Bertaggia Calderara, Debora Bisig, Bettina Duchosal, Michel A. Arbesú, Guillermo Alberio, Lorenzo Heller, Paula Graciela Savoia, Anna |
author |
Bottega, Roberta |
author_facet |
Bottega, Roberta Nicchia, Elena Alfano, Caterina Glembotsky, Ana Claudia Pastore, Annalisa Bertaggia Calderara, Debora Bisig, Bettina Duchosal, Michel A. Arbesú, Guillermo Alberio, Lorenzo Heller, Paula Graciela Savoia, Anna |
author_role |
author |
author2 |
Nicchia, Elena Alfano, Caterina Glembotsky, Ana Claudia Pastore, Annalisa Bertaggia Calderara, Debora Bisig, Bettina Duchosal, Michel A. Arbesú, Guillermo Alberio, Lorenzo Heller, Paula Graciela Savoia, Anna |
author2_role |
author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Nbeal2 Gray Platelet Syndrome Platelets Mutations |
topic |
Nbeal2 Gray Platelet Syndrome Platelets Mutations |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.3 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Gray platelet syndrome (GPS) is a rare inherited macrothrombocytopenia characterized by reduction of a-granules in platelets and megakaryocytes associated with mild-tomoderate bleeding and myelofibrosis [1]. As reported in at least 28 unrelated families [1], GPS is caused by mutations of NBEAL2, the gene encoding for the neurobeachin-like-2 protein. NBEAL2 is a member of the family containing the BEACH (BEige And Chediak Higashi) domain, a conserved region involved in vesicular trafficking that may be critical for the a-granule development [2]. Here, we report novel mutations of NBEAL2 in two affected individuals (P1 and P2), who were previously diagnosed with immune thrombocytopenia (ITP) and then suspected to have GPS because of absence of azurophilic granules on May-Grunwald-Giemsa staining. In P1, sequencing analysis identified an € homozygous missense variant (c.6212G > C; p.Arg2071Pro; Supporting Information Fig. S1). Since her parents were not available for the segregation analysis, we hypothesised that the two mutant alleles were identical by descent because of homozygosity of all the polymorphic markers at the NBEAL2 locus (data not shown). Moreover, the potential hemizygous condition was excluded using statistical analyses of NBEAL2 amplicon coverage as previously reported (Supporting Information Fig. S1C) [3]. In P2, we detected one maternal nonsense (c.3839C > T; p.Arg1280*) and one paternal missense (c.6477C > G; p.His2159Gln; Supporting Information Fig. S1). The three NBEAL2 variants are reported in SNPs databases but with a minor allele frequency <0.01%. Fil: Bottega, Roberta. Università degli Studi di Trieste; Italia Fil: Nicchia, Elena. Università degli Studi di Trieste; Italia Fil: Alfano, Caterina. King's College London; Reino Unido Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Pastore, Annalisa. King's College London; Reino Unido Fil: Bertaggia Calderara, Debora. Universite de Lausanne; Suiza Fil: Bisig, Bettina. Universite de Lausanne; Suiza Fil: Duchosal, Michel A.. Universite de Lausanne; Suiza Fil: Arbesú, Guillermo. Hospital Pediátrico Dr. Humberto Notti; Argentina Fil: Alberio, Lorenzo. Universite de Lausanne; Suiza Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Savoia, Anna. Università degli Studi di Trieste; Italia. Institute for Maternal and Child Health; Italia |
description |
Gray platelet syndrome (GPS) is a rare inherited macrothrombocytopenia characterized by reduction of a-granules in platelets and megakaryocytes associated with mild-tomoderate bleeding and myelofibrosis [1]. As reported in at least 28 unrelated families [1], GPS is caused by mutations of NBEAL2, the gene encoding for the neurobeachin-like-2 protein. NBEAL2 is a member of the family containing the BEACH (BEige And Chediak Higashi) domain, a conserved region involved in vesicular trafficking that may be critical for the a-granule development [2]. Here, we report novel mutations of NBEAL2 in two affected individuals (P1 and P2), who were previously diagnosed with immune thrombocytopenia (ITP) and then suspected to have GPS because of absence of azurophilic granules on May-Grunwald-Giemsa staining. In P1, sequencing analysis identified an € homozygous missense variant (c.6212G > C; p.Arg2071Pro; Supporting Information Fig. S1). Since her parents were not available for the segregation analysis, we hypothesised that the two mutant alleles were identical by descent because of homozygosity of all the polymorphic markers at the NBEAL2 locus (data not shown). Moreover, the potential hemizygous condition was excluded using statistical analyses of NBEAL2 amplicon coverage as previously reported (Supporting Information Fig. S1C) [3]. In P2, we detected one maternal nonsense (c.3839C > T; p.Arg1280*) and one paternal missense (c.6477C > G; p.His2159Gln; Supporting Information Fig. S1). The three NBEAL2 variants are reported in SNPs databases but with a minor allele frequency <0.01%. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02 |
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/11336/47272 Bottega, Roberta; Nicchia, Elena; Alfano, Caterina; Glembotsky, Ana Claudia; Pastore, Annalisa; et al.; Gray platelet syndrome: Novel mutations of the NBEAL2 gene; Wiley-liss, Div John Wiley & Sons Inc; American Journal Of Hematology; 92; 2; 2-2017; E20-E22 0361-8609 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/47272 |
identifier_str_mv |
Bottega, Roberta; Nicchia, Elena; Alfano, Caterina; Glembotsky, Ana Claudia; Pastore, Annalisa; et al.; Gray platelet syndrome: Novel mutations of the NBEAL2 gene; Wiley-liss, Div John Wiley & Sons Inc; American Journal Of Hematology; 92; 2; 2-2017; E20-E22 0361-8609 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1002/ajh.24610 info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.24610 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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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 |
Wiley-liss, Div John Wiley & Sons Inc |
publisher.none.fl_str_mv |
Wiley-liss, Div John Wiley & Sons Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.13397 |