Scientific visits to the Aland Islands.

Area of Science:

• Hematology
• Genetics
• Molecular Biology

Background:

• Von Willebrand's disease (vWD) is a bleeding disorder with historical descriptions dating back to von Willebrand.
• Previous research established distinct forms of vWD and related platelet function defects.

Purpose of the Study:

• To investigate the genetic basis of von Willebrand's disease (vWD) in families from the Aland Islands and compare it to Swedish patients.
• To identify specific mutations in the von Willebrand factor (vWF) gene associated with vWD.

Main Methods:

• Screening of vWF gene 'hot spot' regions (exons 18, 28, 32, 43, 45) for mutations.
• Linkage analysis and genealogical studies to determine the origin of identified mutations.
• Analysis of potential recombination events between the vWF gene and its pseudogene.

Main Results:

• A cytosine deletion in exon 18 of the vWF gene was found in all studied families, suggesting a common origin with Swedish patients.
• Two transitions (G-->A at S1263 and C-->T at P1266) in exon 28 were identified in one individual and their children.
• These transitions in exon 28 are likely due to recombination with the vWF pseudogene.

Conclusions:

• A specific cytosine deletion in exon 18 of the vWF gene is a key mutation in von Willebrand's disease in these populations.
• Recombination events with the vWF pseudogene may contribute to vWF gene mutations.
• Genetic studies confirm a shared origin for vWD mutations in the Aland Islands and Sweden.