A GP1BA Variant in a Czech Family with Monoallelic Bernard-Soulier Syndrome.
Int J Mol Sci
; 23(2)2022 Jan 14.
Article
em En
| MEDLINE
| ID: mdl-35055070
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_000173c.98G > Ap.C33Y), segregating with the macrothrombocytopenia, was detected by whole-exome sequencing. In silico analysis of the protein structure of the novel GPIbα 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
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Variação Genética
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Síndrome de Bernard-Soulier
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Complexo Glicoproteico GPIb-IX de Plaquetas
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Predisposição Genética para Doença
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Alelos
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Female
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Humans
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Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2022
Tipo de documento:
Article