A Novel Homozygous ITGA2B Variant Associated With Recurrent Epistaxis in a Four-Year-Old Girl: A Case Report

TL;DR

A four-year-old girl with recurrent nosebleeds was found to have a new genetic mutation linked to a rare bleeding disorder called Glanzmann thrombasthenia.

Contribution

The study reports a novel homozygous ITGA2B missense variant (c.655G>T; p.Gly219Cys) associated with Glanzmann thrombasthenia.

Findings

Whole-exome sequencing identified a novel homozygous ITGA2B variant absent from public genomic databases.

The variant was predicted to be deleterious by multiple in-silico tools, supporting a diagnosis of Glanzmann thrombasthenia.

The case highlights the importance of genetic testing in diagnosing unexplained mucocutaneous bleeding, especially in consanguineous families.

Abstract

Glanzmann thrombasthenia (GT) is a rare, autosomal recessive platelet aggregation disorder caused by mutations in the ITGA2B and ITGB3 genes. These mutations result in quantitative or qualitative deficiencies in the alpha IIb beta 3 integrin complex, impairing platelet aggregation and leading to recurrent mucocutaneous bleeding. The key findings include absent or severely reduced platelet aggregation with adenosine diphosphate (ADP), epinephrine, and collagen, while aggregation with ristocetin remains normal. While hundreds of pathogenic variants have been identified, the genetic landscape of GT continues to expand with the discovery of novel mutations. GT treatment focuses on controlling bleeding. Hemopoietic stem cell transplantation (HSCT) offers a curative option for severe cases, while gene therapy is a promising future approach. Here, we report the case of a four-year-old female presenting with recurrent bilateral epistaxis and a significant family history of bleeding diathesis. Whole-exome sequencing (WES) revealed a novel homozygous missense variant in ITGA2B (c.655G>T; p.Gly219Cys). This variant, which is absent from public genomic databases, was predicted to be deleterious by multiple in-silico computational tools, supporting a diagnosis of GT. This case identifies a previously unreported pathogenic variant and underscores the critical role of genetic testing in diagnosing unexplained mucocutaneous bleeding, particularly in cases involving consanguinity.

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