Novel point mutation in the leucine-rich motif of the platelet glycoprotein IX associated with Bernard-Soulier syndrome

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder which is caused by a qualitative or quantitative abnormality of the platelet glycoprotein (GP) Ib/IX/V complex. We examined a patient with BSS to find a molecular basis for the defect underlying this disease. The propositus was a 39-year-old Japanese female with life-long bleeding diathesis. Sequence analysis of the GPIX gene revealed a T → C point mutation at nucleotide 1856 (EMBL, M80478), resulting in Phe⁵⁵(TTT) → Ser(TCT) replacement. This substitution created a new Mnl I restriction site in the mutant allele. Restriction analysis revealed that the propositus was homozygous for this sequence, and the same mutation was not detected in 57 unrelated Japanese subjects. Since this mutation is located in the leucine-rich motif (LRM) of the GPIX polypeptide, the Phe⁵⁵ → Ser substitution may result in an alteration of the LRM which leads to the impaired surface expression of GPIb/IX/V complex, a characteristic of BSS.