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Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome

Background: Bernard–Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the GP1BA, GP1BB, or GP9 genes, which together encode the platelet surface receptor glycoprotein comp...

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Autores principales: Minkov, Milen, Zeitlhofer, Petra, Zoubek, Andreas, Kager, Leo, Panzer, Simon, Haas, Oskar A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864212/
https://www.ncbi.nlm.nih.gov/pubmed/33553065
http://dx.doi.org/10.3389/fped.2020.589812
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author Minkov, Milen
Zeitlhofer, Petra
Zoubek, Andreas
Kager, Leo
Panzer, Simon
Haas, Oskar A.
author_facet Minkov, Milen
Zeitlhofer, Petra
Zoubek, Andreas
Kager, Leo
Panzer, Simon
Haas, Oskar A.
author_sort Minkov, Milen
collection PubMed
description Background: Bernard–Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the GP1BA, GP1BB, or GP9 genes, which together encode the platelet surface receptor glycoprotein complex GPIb-IX-V. Objectives: We report two novel heterozygous mutations in the GP1BA and the GP9 genes, respectively. Patients/Methods: We analyzed the platelet glycoprotein expression by flow cytometry and screened the relevant genes for responsible mutations in two unrelated families. Results: Flow cytometric analyses revealed the absence of CD42a (GPIX) and CD42b (GPIb) on the platelets in the two affected siblings of family 1 and a significantly reduced expression of CD42b (GPIb) in the patient of family 2. In the two siblings, we identified a known frameshift (c.1601_1602delAT) and a novel nonsense mutation (c.1036C>T) in the GP1BA gene that abrogated the production of GP1bα. In the other patient, we found a novel missense mutation (c.112T>C) that was co-inherited with a common one (c.182A>G) in the GP9 gene, respectively. All analyzed heterozygous carriers were asymptomatic and had a normal GPIb-IX-V expression. Conclusions: The two novel GP1BA and GP9 mutations reported herein increment the number of causative genetic defects in BSS.
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spelling pubmed-78642122021-02-06 Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome Minkov, Milen Zeitlhofer, Petra Zoubek, Andreas Kager, Leo Panzer, Simon Haas, Oskar A. Front Pediatr Pediatrics Background: Bernard–Soulier Syndrome (BSS) is a rare autosomal recessive bleeding disorder with large platelets and thrombocytopenia. It is caused by homozygous or compound heterozygous mutations in the GP1BA, GP1BB, or GP9 genes, which together encode the platelet surface receptor glycoprotein complex GPIb-IX-V. Objectives: We report two novel heterozygous mutations in the GP1BA and the GP9 genes, respectively. Patients/Methods: We analyzed the platelet glycoprotein expression by flow cytometry and screened the relevant genes for responsible mutations in two unrelated families. Results: Flow cytometric analyses revealed the absence of CD42a (GPIX) and CD42b (GPIb) on the platelets in the two affected siblings of family 1 and a significantly reduced expression of CD42b (GPIb) in the patient of family 2. In the two siblings, we identified a known frameshift (c.1601_1602delAT) and a novel nonsense mutation (c.1036C>T) in the GP1BA gene that abrogated the production of GP1bα. In the other patient, we found a novel missense mutation (c.112T>C) that was co-inherited with a common one (c.182A>G) in the GP9 gene, respectively. All analyzed heterozygous carriers were asymptomatic and had a normal GPIb-IX-V expression. Conclusions: The two novel GP1BA and GP9 mutations reported herein increment the number of causative genetic defects in BSS. Frontiers Media S.A. 2021-01-22 /pmc/articles/PMC7864212/ /pubmed/33553065 http://dx.doi.org/10.3389/fped.2020.589812 Text en Copyright © 2021 Minkov, Zeitlhofer, Zoubek, Kager, Panzer and Haas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Minkov, Milen
Zeitlhofer, Petra
Zoubek, Andreas
Kager, Leo
Panzer, Simon
Haas, Oskar A.
Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome
title Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome
title_full Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome
title_fullStr Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome
title_full_unstemmed Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome
title_short Novel Compound Heterozygous Mutations in Two Families With Bernard–Soulier Syndrome
title_sort novel compound heterozygous mutations in two families with bernard–soulier syndrome
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864212/
https://www.ncbi.nlm.nih.gov/pubmed/33553065
http://dx.doi.org/10.3389/fped.2020.589812
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