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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F18%3A00106258" target="_blank" >RIV/00216224:14740/18:00106258 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/18:00069057

Výsledek na webu

<a href="http://dx.doi.org/10.1080/09537104.2018.1529300" target="_blank" >http://dx.doi.org/10.1080/09537104.2018.1529300</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/09537104.2018.1529300" target="_blank" >10.1080/09537104.2018.1529300</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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&gt;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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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&gt;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Platelets

ISSN

0953-7104

e-ISSN

—

Svazek periodika

29

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

827-833

Kód UT WoS článku

000455589300016

EID výsledku v databázi Scopus

2-s2.0-85055273991