Clinical and genetic aspects of XXXX : searching for genotype/phenotype correlations.

@entity1 @entity3742 @entity548 @entity1423 @entity882 @entity8325 @entity31088 @entity17432 @entity27463 @entity2880
BACKGROUND: @entity3742 is a severe @entity548 disease due to a defect of GPIb/IX/V, a platelet complex that binds the @entity2880 factor. Due to the rarity of the disease, there are reports only on a few cases compromising any attempt to establish correlations between genotype and phenotype. In order to identify any associations, we describe the largest case series ever reported, which was evaluated systematically at the same center. DESIGN AND METHODS: Thirteen @entity1 with the disease and seven obligate carriers were enrolled. We collected clinical aspects and determined platelet features, including number and size, expression of membrane glycoproteins, and @entity8325 induced @entity1423 . Mutations were identified by direct sequencing of the @entity27463 , @entity31088 , and @entity17432 genes and their effect was shown by molecular modeling analyses. RESULTS: @entity1 all had a moderate @entity882 with giant platelets and a @entity548 tendency whose severity varied among individuals. Consistent with expression levels of @entity27463 always lower than 10% of control values, @entity1423 was absent or severely reduced. Homozygous mutations were identified in the @entity27463 , @entity31088 and @entity17432 genes; six were novel alterations expected to destabilize the conformation of the respective protein. Except for obligate carriers of a @entity17432 mutation with a reduced GPIb/IX/V expression and @entity1423 , all the other carriers had no obvious anomalies. CONCLUSIONS: Regardless of mutations identified, the @entity1 ' @entity548 diathesis did not correlate with @entity882 , which was always moderate, and platelet @entity27463 expression, which was always severely impaired. Obligate carriers had features similar to controls though their GPIb/IX/V expression showed discrepancies. Aware of the limitations of our cohort, we cannot define any correlations. However, further investigations should be encouraged to better understand the causes of this rare and underestimated disease.
