A rare case of Glanzmann's thrombasthenia and factor VII deficiency due to a combination of pathogenic and non‐pathogenic gene variants

Abstract

Gp IX (%)99.2Factor VII:C (IU/dL) 22Factor IX:C (IU/dL) 135 F7 genotype Homozygous c.-323_313insCCTATATCCT -122T>C and R353Q polymorphisms ITGB3 genotype Heterozygous variants Q158L and K676T Note: Normal range (NR) for coagulation factors: 50%-150%. | e27LETTER TO THE EDITOR one diagnosis, no further tests are performed. This leads to incomplete diagnosis on most of the occasions. The second interesting point which needs to be highlighted is that it is a practice to attribute the factor deficiency to a pathogenic variant either by referring to the mutation database or with the help of bioinformatic tools. The case clearly shows that mild to moderate deficiencies of factor VII may not always be attributed to pathogenic mutations but may manifest phenotypically when a patient carries multiple polymorphic variants associated with reduced factor VII levels. The case also highlights the need for a comprehensive diagnosis in cases where there is a discrepancy between the laboratory results and the clinical phenotype. This is not only important for treatment but also for an accurate carrier and prenatal diagnosis in case of severe deficiencies.

Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?

“… 107 It is becoming more and more clear that bleeding in GT depends not only on the mutations that define the pathology but involves variants of a wide variety of genes involving coagulation factors and the vasculature as previously discussed for other IPDs. 77 , 78 For example, Deshpande et al 108 identified a combination of GT and mild FVII deficiency in a 13-yr-old Indian boy with GT and a moderately severe bleeding syndrome. His platelets lacked αIIbβ3 due to compound heterozygosity for p.Q132K and p.K650T in ITGB3 .…”