Novel Mutation in Bernard-Soulier Syndrome

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Bernard-Soulier syndrome (BSS) is a severe inherited bleeding disorder.
• It is characterized by low platelet counts, abnormal platelet function, and poor platelet adhesion.
• BSS is caused by genetic defects in the platelet glycoprotein (GP) Ib/IX/V complex.

Purpose of the Study:

• To investigate the genetic cause of BSS in a patient with a typical phenotype.
• To identify the specific mutation responsible for the absence of GPIb/IX/V receptor expression.

Main Methods:

• Phenotypic analysis including platelet count, morphology, and bleeding symptoms.
• Flow cytometry to assess platelet receptor surface expression (GPIb/IX/V).
• Immunofluorescence microscopy for GPIX staining.
• Molecular genetic analysis to identify gene mutations.

Main Results:

• The patient presented with classic BSS symptoms but was diagnosed late (age 39).
• Platelet analysis showed absent GPIb/IX/V receptor expression and minimal GPIX staining.
• A novel homozygous 11-nucleotide deletion (g.1644_1654del11) in the GPIX gene was identified.

Conclusions:

• The identified homozygous deletion in the GPIX gene is the causative mutation for BSS in this patient.
• This deletion affects the Kozak sequence and start codon, inhibiting functional GPIX protein synthesis.
• The findings highlight the importance of genetic analysis in diagnosing rare bleeding disorders like BSS.