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, vol. 23, No 2, p. 1-13. ISSN 1422-0067. doi:10.3390/ijms23020885. 2022.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30205 Hematology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW 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
Tags 14110212, 14110230, 14110323, 14110616, CF CRYO, CF GEN, podil, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 3/4/2023 09:55.
Abstract
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 projectName: Analýza českých genomů pro teranostiku
LM2018127, research and development projectName: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LM2018132, research and development projectName: Národní centrum lékařské genomiky (Acronym: NCLG)
Investor: Ministry of Education, Youth and Sports of the CR, National Center for Medical Genomics
MUNI/A/1330/2021, interní kód MUName: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit IX (Acronym: VýDiTeHeMa IX)
Investor: Masaryk University
MUNI/11/SUP/22/2020, interní kód MUName: Zavedení technologie CRISPR/Cas9 pro funkční studie u familiárních hematopoetických onemocnění
Investor: Masaryk University
NU20-08-00137, research and development projectName: 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
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