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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/47272
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/47272
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-09-29T09:48:07Zoai: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:34982025-09-29 09:48:08.002CONICET 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/
eu_rights_str_mv 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
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 13.069144

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