Hereditary multiple and isolated sporadic exostoses in the same kindred: identification of the causative gene ( XXXX ) and detection of a new mutation, @entity70568 , that distinguishes the two phenotypes.

@entity511 @entity70568 @entity18215 @entity74 @entity18216 @entity5607 @entity5608
@entity5607 ( @entity5607 ) is a well known @entity74 . Isolated exostoses, on the other hand, occur as sporadic events or as secondary post-traumatic sequel. The occurrence of solitary exostoses in individuals from pedigrees affected with @entity5607 may distort conclusions about carrier status and/or diagnosis. Both conditions are potentially malignant and both are associated with genetic alterations in either @entity18215 or @entity18216 genes. In this study, we present a seven-generation family from western Sweden consisting of 170 blood relatives, 38 of whom had multiple cartilaginous exostoses, while 8 had isolated exostoses. Linkage analysis aimed to discern one of the known @entity5608 genes demonstrated linkage of the @entity5607 phenotype to the @entity18216 gene. Subsequent mutation analysis revealed a novel mutation, @entity70568 , in this gene. All carriers of the detected mutation had multiple exostoses, indicating full penetrance. None of the pedigree members with isolated exostoses were carriers of the detected mutation. Two of the mutation carriers developed @entity511 yielding a 5.2% risk of malignant development for this mutation. The detection of this mutation has enabled us to provide appropriate genetic counseling concerning this complex situation.
