BACKGROUND: Bernard-Soulier syndrome (BSS) is a severe congenital bleeding disorder characterized by thrombocytopenia, thrombocytopathy and decreased platelet adhesion. BSS results from genetic alterations of the glycoprotein (GP) Ib/IX/V complex. METHODS: We report on a patient demonstrating typical BSS phenotype (thrombocytopenia with giant platelets, bleeding symptoms). However, BSS was not diagnosed until he reached the age of 39 years. RESULTS: Flow cytometry of the patient's platelets revealed absence of GPIb/IX/V receptor surface expression. In addition, immunofluorescence analysis of patient's platelets demonstrated very faint staining of GPIX. A novel homozygous deletion comprising 11 nucleotides starting at position 1644 of the GPIX gene was identified using molecular genetic analysis. CONCLUSIONS: The novel 11-nucleotide deletion (g.1644_1654del11) was identified as causing the bleeding disorder in the BSS patient. This homozygous deletion includes the last 4 nucleotides of the Kozak sequence as well as the start codon and the following 4 nucleotides of the coding sequence. The Kozak sequence is a region indispensable for the initiation of the protein translation process, thus preventing synthesis of functional GPIX protein in the case of deletion.
BACKGROUND: Bernard-Soulier syndrome (BSS) is a severe congenital bleeding disorder characterized by thrombocytopenia, thrombocytopathy and decreased platelet adhesion. BSS results from genetic alterations of the glycoprotein (GP) Ib/IX/V complex. METHODS: We report on a patient demonstrating typical BSS phenotype (thrombocytopenia with giant platelets, bleeding symptoms). However, BSS was not diagnosed until he reached the age of 39 years. RESULTS: Flow cytometry of the patient's platelets revealed absence of GPIb/IX/V receptor surface expression. In addition, immunofluorescence analysis of patient's platelets demonstrated very faint staining of GPIX. A novel homozygous deletion comprising 11 nucleotides starting at position 1644 of the GPIX gene was identified using molecular genetic analysis. CONCLUSIONS: The novel 11-nucleotide deletion (g.1644_1654del11) was identified as causing the bleeding disorder in the BSS patient. This homozygous deletion includes the last 4 nucleotides of the Kozak sequence as well as the start codon and the following 4 nucleotides of the coding sequence. The Kozak sequence is a region indispensable for the initiation of the protein translation process, thus preventing synthesis of functional GPIX protein in the case of deletion.
Authors: C Meisel; V Afshar-Kharghan; I Cascorbi; M Laule; V Stangl; S B Felix; G Baumann; J A López; I Roots; K Stangl Journal: J Am Coll Cardiol Date: 2001-10 Impact factor: 24.094
Authors: Gabriele Jedlitschky; Konstanze Tirschmann; Lena E Lubenow; Hendrik K Nieuwenhuis; Jan W N Akkerman; Andreas Greinacher; Heyo K Kroemer Journal: Blood Date: 2004-08-05 Impact factor: 22.113