A novel germline mutation in GP1BA gene N-terminal domain in
monoallelic Bernard-Soulier syndrome

J 2018

A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome

TRIZULJAK, Jakub, Kateřina STAŇO KOZUBÍK, Lenka RADOVÁ, Michaela PEŠOVÁ, Karol PÁL et. al.

Basic information

Original name

A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome

Authors

TRIZULJAK, Jakub (703 Slovakia, belonging to the institution), Kateřina STAŇO KOZUBÍK (203 Czech Republic, belonging to the institution), Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Michaela PEŠOVÁ (203 Czech Republic, belonging to the institution), Karol PÁL (703 Slovakia, belonging to the institution), Kamila RÉBLOVÁ (203 Czech Republic, belonging to the institution), Olga STEHLÍKOVÁ (203 Czech Republic, belonging to the institution), Petr SMEJKAL (203 Czech Republic, belonging to the institution), Jiřina ZAVŘELOVÁ (203 Czech Republic, belonging to the institution), M. PACEJKA (203 Czech Republic), Jiří MAYER (203 Czech Republic, belonging to the institution), Šárka POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution) and Michael DOUBEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Platelets, PHILADELPHIA, TAYLOR & FRANCIS INC, 2018, 0953-7104

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.106

RIV identification code

RIV/00216224:14740/18:00106258

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1080/09537104.2018.1529300

UT WoS

000455589300016

Keywords in English

Autosomal dominant variant; GP1BA; Inherited thrombocytopenia; monoallelic Bernard-Soulier syndrome

Abstract

V originále

Mutations in the GP1BA gene have been associated with platelet-type von Willebrand disease and Bernard-Soulier syndrome. Here, we report a novel GP1BA mutation in a family with autosomal dominant macrothrombocytopenia and mild bleeding. We performed analyses of seven family members. Using whole-exome sequencing of germline DNA samples, we identified a heterozygous single-nucleotide change in GP1BA (exone2:c.176T>G), encoding a p.Leu59Arg substitution in the N-terminal domain, segregating with macrothrombocytopenia. This variant has not been previously reported. We also analysed the structure of the detected sequence variant in silica In particular, we used the crystal structure of the human platelet receptor GP lba N-terminal domain. Replacement of aliphatic amino-acid Leu 59 with charged, polar and larger arginine probably disrupts the protein structure. An autosomal dominant mode of inheritance, a family history of mild bleeding episodes, aggregation pattern in affected individuals together with evidence of mutation occurring in part of the GP1BA gene encoding the leucine-rich repeat region suggest a novel variant causing monoallelic Bernard-Soulier syndrome.

Links

LM2015091, research and development project

Name: Národní centrum lékařské genomiky (Acronym: NCLG)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

NV16-29447A, research and development project

Name: Vyhledávání mutací predisponujících k familiárním hematologickým a onkologickým onemocněním

Citovat

TRIZULJAK, Jakub, Kateřina STAŇO KOZUBÍK, Lenka RADOVÁ, Michaela PEŠOVÁ, Karol PÁL, Kamila RÉBLOVÁ, Olga STEHLÍKOVÁ, Petr SMEJKAL, Jiřina ZAVŘELOVÁ, M. PACEJKA, Jiří MAYER, Šárka POSPÍŠILOVÁ and Michael DOUBEK. A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome. Platelets. PHILADELPHIA: TAYLOR & FRANCIS INC, 2018, vol. 29, No 8, p. 827-833. ISSN 0953-7104. Available from: https://dx.doi.org/10.1080/09537104.2018.1529300.

@article{1498777,
   author = {Trizuljak, Jakub and Staňo Kozubík, Kateřina and Radová, Lenka and Pešová, Michaela and Pál, Karol and Réblová, Kamila and Stehlíková, Olga and Smejkal, Petr and Zavřelová, Jiřina and Pacejka, M. and Mayer, Jiří and Pospíšilová, Šárka and Doubek, Michael},
   article_location = {PHILADELPHIA},
   article_number = {8},
   doi = {http://dx.doi.org/10.1080/09537104.2018.1529300},
   keywords = {Autosomal dominant variant; GP1BA; Inherited thrombocytopenia; monoallelic Bernard-Soulier syndrome},
   language = {eng},
   issn = {0953-7104},
   journal = {Platelets},
   title = {A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome},
   url = {https://www.tandfonline.com/doi/full/10.1080/09537104.2018.1529300},
   volume = {29},
   year = {2018}
}

TY  - JOUR
ID  - 1498777
AU  - Trizuljak, Jakub - Staňo Kozubík, Kateřina - Radová, Lenka - Pešová, Michaela - Pál, Karol - Réblová, Kamila - Stehlíková, Olga - Smejkal, Petr - Zavřelová, Jiřina - Pacejka, M. - Mayer, Jiří - Pospíšilová, Šárka - Doubek, Michael
PY  - 2018
TI  - A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome
JF  - Platelets
VL  - 29
IS  - 8
SP  - 827-833
EP  - 827-833
PB  - TAYLOR & FRANCIS INC
SN  - 09537104
KW  - Autosomal dominant variant
KW  - GP1BA
KW  - Inherited thrombocytopenia
KW  - monoallelic Bernard-Soulier syndrome
UR  - https://www.tandfonline.com/doi/full/10.1080/09537104.2018.1529300
N2  - Mutations in the GP1BA gene have been associated with platelet-type von Willebrand disease and Bernard-Soulier syndrome. Here, we report a novel GP1BA mutation in a family with autosomal dominant macrothrombocytopenia and mild bleeding. We performed analyses of seven family members. Using whole-exome sequencing of germline DNA samples, we identified a heterozygous single-nucleotide change in GP1BA (exone2:c.176T>G), encoding a p.Leu59Arg substitution in the N-terminal domain, segregating with macrothrombocytopenia. This variant has not been previously reported. We also analysed the structure of the detected sequence variant in silica In particular, we used the crystal structure of the human platelet receptor GP lba N-terminal domain. Replacement of aliphatic amino-acid Leu 59 with charged, polar and larger arginine probably disrupts the protein structure. An autosomal dominant mode of inheritance, a family history of mild bleeding episodes, aggregation pattern in affected individuals together with evidence of mutation occurring in part of the GP1BA gene encoding the leucine-rich repeat region suggest a novel variant causing monoallelic Bernard-Soulier syndrome.
ER  -

TRIZULJAK, Jakub, Kateřina STAŇO KOZUBÍK, Lenka RADOVÁ, Michaela PEŠOVÁ, Karol PÁL, Kamila RÉBLOVÁ, Olga STEHLÍKOVÁ, Petr SMEJKAL, Jiřina ZAVŘELOVÁ, M. PACEJKA, Jiří MAYER, Šárka POSPÍŠILOVÁ and Michael DOUBEK. A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome. \textit{Platelets}. PHILADELPHIA: TAYLOR \&{}amp; FRANCIS INC, 2018, vol.~29, No~8, p.~827-833. ISSN~0953-7104. Available from: https://dx.doi.org/10.1080/09537104.2018.1529300.

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