A GP1BA Variant in a Czech Family with Monoallelic
Bernard-Soulier Syndrome

J 2022

A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome

SKALNÍKOVÁ, Magdalena, Kateřina STAŇO KOZUBÍK, Jakub TRIZULJAK, Zuzana VRZALOVÁ, Lenka RADOVÁ et. al.

Basic information

Original name

A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome

Authors

SKALNÍKOVÁ, Magdalena (203 Czech Republic, guarantor, belonging to the institution), Kateřina STAŇO KOZUBÍK (203 Czech Republic, belonging to the institution), Jakub TRIZULJAK (703 Slovakia, belonging to the institution), Zuzana VRZALOVÁ (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Kamila RÉBLOVÁ (203 Czech Republic, belonging to the institution), Radka HOLBOVÁ (203 Czech Republic, belonging to the institution), Terézia KURUCOVÁ (703 Slovakia, belonging to the institution), Hana SVOZILOVÁ (203 Czech Republic, belonging to the institution), Jiří ŠTIKA (203 Czech Republic, belonging to the institution), Ivona BLAHÁKOVÁ (203 Czech Republic, belonging to the institution), Barbara DVOŘÁČKOVÁ (203 Czech Republic, belonging to the institution), Marie PRUDKOVÁ (203 Czech Republic, belonging to the institution), Olga STEHLÍKOVÁ (203 Czech Republic, belonging to the institution), Michal ŠMÍDA (203 Czech Republic, belonging to the institution), Leoš KŘEN (203 Czech Republic, belonging to the institution), Petr SMEJKAL (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Michael DOUBEK (203 Czech Republic, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2022, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.600

RIV identification code

RIV/00216224:14740/22:00126142

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/ijms23020885

UT WoS

000757390400001

Keywords in English

Bernard-Soulier syndrome; monoallelic; autosomal dominant; GP1BA; macrothrombocytopenia

Abstract

V originále

Bernard-Soulier syndrome (BSS) is a rare inherited disorder characterized by unusually large platelets, low platelet count, and prolonged bleeding time. BSS is usually inherited in an autosomal recessive (AR) mode of inheritance due to a deficiency of the GPIb-IX-V complex also known as the von Willebrand factor (VWF) receptor. We investigated a family with macrothrombocytopenia, a mild bleeding tendency, slightly lowered platelet aggregation tests, and suspected autosomal dominant (AD) inheritance. We have detected a heterozygous GP1BA likely pathogenic variant, causing monoallelic BSS. A germline GP1BA gene variant (NM_000173:c.98G > A:p.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIb alpha variant revealed a potential structural defect, which could impact proper protein folding and subsequent binding to VWF. Flow cytometry, immunoblot, and electron microscopy demonstrated further differences between p.C33Y GP1BA carriers and healthy controls. Here, we provide a detailed insight into its clinical presentation and phenotype. Moreover, the here described case first presents an mBSS patient with two previous ischemic strokes.

Links

EF16_026/0008448, research and development project

Name: Analýza českých genomů pro teranostiku

MUNI/A/1330/2021, interní kód MU

Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit IX (Acronym: VýDiTeHeMa IX)

Investor: Masaryk University

MUNI/11/SUP/22/2020, interní kód MU

Name: Zavedení technologie CRISPR/Cas9 pro funkční studie u familiárních hematopoetických onemocnění

Investor: Masaryk University

NU20-08-00137, research and development project

Name: Vyhledávání a funkční testování variant genů predisponujících k familiárním onemocněním krvetvorby

Investor: Ministry of Health of the CR, Searching and functional testing of gene variants predisposing to familial haematopoietic disorders, Subprogram 1 - standard

90127, large research infrastructures

Name: CIISB II

90132, large research infrastructures

Name: NCMG II

Citovat

SKALNÍKOVÁ, Magdalena, Kateřina STAŇO KOZUBÍK, Jakub TRIZULJAK, Zuzana VRZALOVÁ, Lenka RADOVÁ, Kamila RÉBLOVÁ, Radka HOLBOVÁ, Terézia KURUCOVÁ, Hana SVOZILOVÁ, Jiří ŠTIKA, Ivona BLAHÁKOVÁ, Barbara DVOŘÁČKOVÁ, Marie PRUDKOVÁ, Olga STEHLÍKOVÁ, Michal ŠMÍDA, Leoš KŘEN, Petr SMEJKAL, Šárka POSPÍŠILOVÁ and Michael DOUBEK. A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol. 23, No 2, p. 1-13. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms23020885.

@article{1863063,
   author = {Skalníková, Magdalena and Staňo Kozubík, Kateřina and Trizuljak, Jakub and Vrzalová, Zuzana and Radová, Lenka and Réblová, Kamila and Holbová, Radka and Kurucová, Terézia and Svozilová, Hana and Štika, Jiří and Blaháková, Ivona and Dvořáčková, Barbara and Prudková, Marie and Stehlíková, Olga and Šmída, Michal and Křen, Leoš and Smejkal, Petr and Pospíšilová, Šárka and Doubek, Michael},
   article_location = {Basel},
   article_number = {2},
   doi = {http://dx.doi.org/10.3390/ijms23020885},
   keywords = {Bernard-Soulier syndrome; monoallelic; autosomal dominant; GP1BA; macrothrombocytopenia},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome},
   url = {https://www.mdpi.com/1422-0067/23/2/885},
   volume = {23},
   year = {2022}
}

TY  - JOUR
ID  - 1863063
AU  - Skalníková, Magdalena - Staňo Kozubík, Kateřina - Trizuljak, Jakub - Vrzalová, Zuzana - Radová, Lenka - Réblová, Kamila - Holbová, Radka - Kurucová, Terézia - Svozilová, Hana - Štika, Jiří - Blaháková, Ivona - Dvořáčková, Barbara - Prudková, Marie - Stehlíková, Olga - Šmída, Michal - Křen, Leoš - Smejkal, Petr - Pospíšilová, Šárka - Doubek, Michael
PY  - 2022
TI  - A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome
JF  - International Journal of Molecular Sciences
VL  - 23
IS  - 2
SP  - 1-13
EP  - 1-13
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - Bernard-Soulier syndrome
KW  - monoallelic
KW  - autosomal dominant
KW  - GP1BA
KW  - macrothrombocytopenia
UR  - https://www.mdpi.com/1422-0067/23/2/885
N2  - Bernard-Soulier syndrome (BSS) is a rare inherited disorder characterized by unusually large platelets, low platelet count, and prolonged bleeding time. BSS is usually inherited in an autosomal recessive (AR) mode of inheritance due to a deficiency of the GPIb-IX-V complex also known as the von Willebrand factor (VWF) receptor. We investigated a family with macrothrombocytopenia, a mild bleeding tendency, slightly lowered platelet aggregation tests, and suspected autosomal dominant (AD) inheritance. We have detected a heterozygous GP1BA likely pathogenic variant, causing monoallelic BSS. A germline GP1BA gene variant (NM_000173:c.98G > A:p.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIb alpha variant revealed a potential structural defect, which could impact proper protein folding and subsequent binding to VWF. Flow cytometry, immunoblot, and electron microscopy demonstrated further differences between p.C33Y GP1BA carriers and healthy controls. Here, we provide a detailed insight into its clinical presentation and phenotype. Moreover, the here described case first presents an mBSS patient with two previous ischemic strokes.
ER  -

SKALNÍKOVÁ, Magdalena, Kateřina STAŇO KOZUBÍK, Jakub TRIZULJAK, Zuzana VRZALOVÁ, Lenka RADOVÁ, Kamila RÉBLOVÁ, Radka HOLBOVÁ, Terézia KURUCOVÁ, Hana SVOZILOVÁ, Jiří ŠTIKA, Ivona BLAHÁKOVÁ, Barbara DVOŘÁČKOVÁ, Marie PRUDKOVÁ, Olga STEHLÍKOVÁ, Michal ŠMÍDA, Leoš KŘEN, Petr SMEJKAL, Šárka POSPÍŠILOVÁ and Michael DOUBEK. A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2022, vol.~23, No~2, p.~1-13. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms23020885.

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