Abstract Number: PB1508
Meeting: ISTH 2020 Congress
Background: Glanzmann´s Thrombasthenia (GT) is a challenging syndrome as platelet receptor expression does not always correlate with the bleeding phenotype. Molecular analysis and variant mapping is proving useful in our understanding of which mutations may have an impact on receptor function as well as total protein expression.
Aims: To further research on rare blood disorders, patients have created forums where they can access knowledgeable providers, educational and diagnostic services. Comprehensive Health and Education Services (CHES) has been a leader in helping families drive genetic sequencing for families with a shared diagnosis, such as the recent Glanzmann’s Retreat in Austin Texas 2019. The aim was to provide molecular diagnosis and variant identification for providers, patients and family members.
Methods: Over 400 individuals with RBD have been evaluated through CHES forms, including 56 individuals with Glanzmann’s or potential carriers. Diagnosis through flow cytometry was performed by the primary physician and whole gene sequencing was performed using a validated Next Generation Sequencing (NGS) clotting protein whole gene panel which contains ITGAIIb and ITGAbeta3 along with 20 additional clotting genes. Each individual had whole gene sequencing on all 22 genes on the panel.
Results: As in previous reports for RBD in the US, we found both compound heterzygotes as well as patients with homozygous variants. Bleeding scores correlated when there was a complete absence of receptors, but varied considerably in the case of the missense mutations. Number of individuals and type of mutations include: missense variants: 39,
frameshifts ITGB3:5-ITGAIIb:11, early stop: 4, splice site variants: 19 deletions or CNV:2, premature start in ITGAIIb: 3, and start loss in ITGB3: 3.
Conclusions: Patient AND family members are critical to determine which molecular variants are pathogenic in rare disorders, particularly FVII deficiency.Patient AND family members are critical to determine which molecular variants are pathogenic in rare disorders, particularly FVII deficiency.
To cite this abstract in AMA style:Nugent D, Williams S, Hoang J, Brewer J. Molecular Insights into Glanzmann’s Thrombasthenia through Family Forums for Gene Sequencing and Discovery [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/molecular-insights-into-glanzmanns-thrombasthenia-through-family-forums-for-gene-sequencing-and-discovery/. Accessed December 11, 2023.
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