Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency
- Autores
- Bottega, Roberta; Pecci, Alessandro; de Candia, Erica; Pujol Moix, Nuria; Heller, Paula Graciela; Noris, Patrizia; de Rocco, Daniela; Podda, Gian Marco; Glembotsky, Ana Claudia; Cattaneo Marco; Balduini, Carlo L.; Savoia, Anna
- Año de publicación
- 2013
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. We studied 11 consecutive families with inherited macrothrombocytopenia of unknown origin and α-granule deficiency. All of them underwent NBEAL2 DNA sequencing and evaluation of the platelet phenotype, including a systematic assessment of the α-granule content by immunofluorescence analysis for α-granule secretory proteins. We identified 9 novel mutations hitting the two alleles of NBEAL2 in 4 probands. They included missense, nonsense and frameshift mutations, as well as nucleotide substitutions that altered the splicing mechanisms as determined at the RNA level. All the individuals with NBEAL2 biallelic mutations showed almost complete absence of platelet α-granules. Interestingly, the 13 individuals assumed to be asymptomatic because carriers of a mutated allele had platelet macrocytosis and significant reduction of the α-granule content. However, they were not thrombocytopenic. In the remaining 7 probands, we did not identify any NBEAL2 alterations, suggesting that other genetic defect(s) are responsible for their platelet phenotype. Of note, these patients were characterized by a lower severity of the α-granule deficiency than individuals with two NBEAL2 mutated alleles. Our data extend the spectrum of mutations responsible for gray platelet syndrome and demonstrate that macrothrombocytopenia with α-granule deficiency is a genetic heterogeneous trait. In terms of practical applications, the screening of NBEAL2 is worthwhile only in patients with macrothrombocytopenia and severe reduction of the α-granules. Finally, individuals carrying one NBEAL2 mutated allele have mild laboratory abnormalities, suggesting that even haploinsufficiency has an effect on platelet phenotype.
Fil: Bottega, Roberta. Università degli Studi di Trieste; Italia
Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia
Fil: de Candia, Erica. Università Cattolica del Sacro Cuore; Argentina
Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España
Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia
Fil: de Rocco, Daniela. No especifíca;
Fil: Podda, Gian Marco. Università degli Studi di Milano; Italia
Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Cattaneo Marco. Università degli Studi di Milano; Italia
Fil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; Italia
Fil: Savoia, Anna. Università degli Studi di Trieste; Italia - Materia
-
Gray Platelet Syndrome
Nbeal2
Thrombospondin 1
Thrombocytopenia - 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:11336/1514
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Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiencyBottega, RobertaPecci, Alessandrode Candia, EricaPujol Moix, NuriaHeller, Paula GracielaNoris, Patriziade Rocco, DanielaPodda, Gian MarcoGlembotsky, Ana ClaudiaCattaneo MarcoBalduini, Carlo L.Savoia, AnnaGray Platelet SyndromeNbeal2Thrombospondin 1Thrombocytopeniahttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. We studied 11 consecutive families with inherited macrothrombocytopenia of unknown origin and α-granule deficiency. All of them underwent NBEAL2 DNA sequencing and evaluation of the platelet phenotype, including a systematic assessment of the α-granule content by immunofluorescence analysis for α-granule secretory proteins. We identified 9 novel mutations hitting the two alleles of NBEAL2 in 4 probands. They included missense, nonsense and frameshift mutations, as well as nucleotide substitutions that altered the splicing mechanisms as determined at the RNA level. All the individuals with NBEAL2 biallelic mutations showed almost complete absence of platelet α-granules. Interestingly, the 13 individuals assumed to be asymptomatic because carriers of a mutated allele had platelet macrocytosis and significant reduction of the α-granule content. However, they were not thrombocytopenic. In the remaining 7 probands, we did not identify any NBEAL2 alterations, suggesting that other genetic defect(s) are responsible for their platelet phenotype. Of note, these patients were characterized by a lower severity of the α-granule deficiency than individuals with two NBEAL2 mutated alleles. Our data extend the spectrum of mutations responsible for gray platelet syndrome and demonstrate that macrothrombocytopenia with α-granule deficiency is a genetic heterogeneous trait. In terms of practical applications, the screening of NBEAL2 is worthwhile only in patients with macrothrombocytopenia and severe reduction of the α-granules. Finally, individuals carrying one NBEAL2 mutated allele have mild laboratory abnormalities, suggesting that even haploinsufficiency has an effect on platelet phenotype.Fil: Bottega, Roberta. Università degli Studi di Trieste; ItaliaFil: Pecci, Alessandro. Universita Degli Studi Di Pavia; ItaliaFil: de Candia, Erica. Università Cattolica del Sacro Cuore; ArgentinaFil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; EspañaFil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Noris, Patrizia. Universita Degli Studi Di Pavia; ItaliaFil: de Rocco, Daniela. No especifíca;Fil: Podda, Gian Marco. Università degli Studi di Milano; ItaliaFil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Cattaneo Marco. Università degli Studi di Milano; ItaliaFil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; ItaliaFil: Savoia, Anna. Università degli Studi di Trieste; ItaliaFerrata Storti Foundation2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/1514Bottega, Roberta; Pecci, Alessandro; de Candia, Erica; Pujol Moix, Nuria; Heller, Paula Graciela; et al.; Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency; Ferrata Storti Foundation; Haematologica; 98; 6; 6-2013; 868-8740390-60781592-8721enginfo:eu-repo/semantics/altIdentifier/doi/10.3324/haematol.2012.075861info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:22Zoai:ri.conicet.gov.ar:11336/1514instacron: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 10:06:22.593CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
title |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
spellingShingle |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency Bottega, Roberta Gray Platelet Syndrome Nbeal2 Thrombospondin 1 Thrombocytopenia |
title_short |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
title_full |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
title_fullStr |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
title_full_unstemmed |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
title_sort |
Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency |
dc.creator.none.fl_str_mv |
Bottega, Roberta Pecci, Alessandro de Candia, Erica Pujol Moix, Nuria Heller, Paula Graciela Noris, Patrizia de Rocco, Daniela Podda, Gian Marco Glembotsky, Ana Claudia Cattaneo Marco Balduini, Carlo L. Savoia, Anna |
author |
Bottega, Roberta |
author_facet |
Bottega, Roberta Pecci, Alessandro de Candia, Erica Pujol Moix, Nuria Heller, Paula Graciela Noris, Patrizia de Rocco, Daniela Podda, Gian Marco Glembotsky, Ana Claudia Cattaneo Marco Balduini, Carlo L. Savoia, Anna |
author_role |
author |
author2 |
Pecci, Alessandro de Candia, Erica Pujol Moix, Nuria Heller, Paula Graciela Noris, Patrizia de Rocco, Daniela Podda, Gian Marco Glembotsky, Ana Claudia Cattaneo Marco Balduini, Carlo L. Savoia, Anna |
author2_role |
author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Gray Platelet Syndrome Nbeal2 Thrombospondin 1 Thrombocytopenia |
topic |
Gray Platelet Syndrome Nbeal2 Thrombospondin 1 Thrombocytopenia |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.2 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. We studied 11 consecutive families with inherited macrothrombocytopenia of unknown origin and α-granule deficiency. All of them underwent NBEAL2 DNA sequencing and evaluation of the platelet phenotype, including a systematic assessment of the α-granule content by immunofluorescence analysis for α-granule secretory proteins. We identified 9 novel mutations hitting the two alleles of NBEAL2 in 4 probands. They included missense, nonsense and frameshift mutations, as well as nucleotide substitutions that altered the splicing mechanisms as determined at the RNA level. All the individuals with NBEAL2 biallelic mutations showed almost complete absence of platelet α-granules. Interestingly, the 13 individuals assumed to be asymptomatic because carriers of a mutated allele had platelet macrocytosis and significant reduction of the α-granule content. However, they were not thrombocytopenic. In the remaining 7 probands, we did not identify any NBEAL2 alterations, suggesting that other genetic defect(s) are responsible for their platelet phenotype. Of note, these patients were characterized by a lower severity of the α-granule deficiency than individuals with two NBEAL2 mutated alleles. Our data extend the spectrum of mutations responsible for gray platelet syndrome and demonstrate that macrothrombocytopenia with α-granule deficiency is a genetic heterogeneous trait. In terms of practical applications, the screening of NBEAL2 is worthwhile only in patients with macrothrombocytopenia and severe reduction of the α-granules. Finally, individuals carrying one NBEAL2 mutated allele have mild laboratory abnormalities, suggesting that even haploinsufficiency has an effect on platelet phenotype. Fil: Bottega, Roberta. Università degli Studi di Trieste; Italia Fil: Pecci, Alessandro. Universita Degli Studi Di Pavia; Italia Fil: de Candia, Erica. Università Cattolica del Sacro Cuore; Argentina Fil: Pujol Moix, Nuria. Universitat Autònoma de Barcelona; España Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Noris, Patrizia. Universita Degli Studi Di Pavia; Italia Fil: de Rocco, Daniela. No especifíca; Fil: Podda, Gian Marco. Università degli Studi di Milano; Italia Fil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Cattaneo Marco. Università degli Studi di Milano; Italia Fil: Balduini, Carlo L.. Universita Degli Studi Di Pavia; Italia Fil: Savoia, Anna. Università degli Studi di Trieste; Italia |
description |
The gray platelet syndrome is a rare inherited bleeding disorder characterized by macrothrombocytopenia and deficiency of alpha (α)-granules in platelets. The genetic defect responsible for gray platelet syndrome was recently identified in biallelic mutations in the NBEAL2 gene. We studied 11 consecutive families with inherited macrothrombocytopenia of unknown origin and α-granule deficiency. All of them underwent NBEAL2 DNA sequencing and evaluation of the platelet phenotype, including a systematic assessment of the α-granule content by immunofluorescence analysis for α-granule secretory proteins. We identified 9 novel mutations hitting the two alleles of NBEAL2 in 4 probands. They included missense, nonsense and frameshift mutations, as well as nucleotide substitutions that altered the splicing mechanisms as determined at the RNA level. All the individuals with NBEAL2 biallelic mutations showed almost complete absence of platelet α-granules. Interestingly, the 13 individuals assumed to be asymptomatic because carriers of a mutated allele had platelet macrocytosis and significant reduction of the α-granule content. However, they were not thrombocytopenic. In the remaining 7 probands, we did not identify any NBEAL2 alterations, suggesting that other genetic defect(s) are responsible for their platelet phenotype. Of note, these patients were characterized by a lower severity of the α-granule deficiency than individuals with two NBEAL2 mutated alleles. Our data extend the spectrum of mutations responsible for gray platelet syndrome and demonstrate that macrothrombocytopenia with α-granule deficiency is a genetic heterogeneous trait. In terms of practical applications, the screening of NBEAL2 is worthwhile only in patients with macrothrombocytopenia and severe reduction of the α-granules. Finally, individuals carrying one NBEAL2 mutated allele have mild laboratory abnormalities, suggesting that even haploinsufficiency has an effect on platelet phenotype. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-06 |
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/11336/1514 Bottega, Roberta; Pecci, Alessandro; de Candia, Erica; Pujol Moix, Nuria; Heller, Paula Graciela; et al.; Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency; Ferrata Storti Foundation; Haematologica; 98; 6; 6-2013; 868-874 0390-6078 1592-8721 |
url |
http://hdl.handle.net/11336/1514 |
identifier_str_mv |
Bottega, Roberta; Pecci, Alessandro; de Candia, Erica; Pujol Moix, Nuria; Heller, Paula Graciela; et al.; Correlation between platelet phenotype and NBEAL2 genotype in patients with congenital thrombocytopenia and α-granule deficiency; Ferrata Storti Foundation; Haematologica; 98; 6; 6-2013; 868-874 0390-6078 1592-8721 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.3324/haematol.2012.075861 |
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 |
Ferrata Storti Foundation |
publisher.none.fl_str_mv |
Ferrata Storti Foundation |
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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1842269955428450304 |
score |
13.13397 |