Mutations in either the EXT1 or EXT2 genes lead to Multiple Osteochondromas (MO), an autosomal dominantly inherited disorder. This is a report on clinical findings and results of molecular analyses of Show more
Mutations in either the EXT1 or EXT2 genes lead to Multiple Osteochondromas (MO), an autosomal dominantly inherited disorder. This is a report on clinical findings and results of molecular analyses of both genes in 23 German patients affected by MO. Mutation screening was performed by using denaturing high performance liquid chromatography (dHPLC) and automated sequencing. In 17 of 23 patients novel pathogenic mutations have been identified; eleven in the EXT1 and six in the EXT2 gene. Five patients were carriers of recurrent mutations in the EXT2 gene (p.Asp227Asn, p.Gln172X, p.Gln258X) and one patient had no detectable mutation. To demonstrate their pathogenic effect on transcription, two complex mutations in EXT1 and EXT2 and three splice site mutations were characterized by mRNA investigations. The results obtained provide evidence for different aberrant splice effects - usage of new cryptic splice sites and exon skipping. Our study extends the mutational spectrum and understanding of pathogenic effects of mutations in EXT1 and EXT2. Show less
Hereditary multiple exostosis (HME), a disorder inherited in an autosomal dominant manner, is characterized by multiple projections of bone, mainly at the extremities. The risk of malignant transforma Show more
Hereditary multiple exostosis (HME), a disorder inherited in an autosomal dominant manner, is characterized by multiple projections of bone, mainly at the extremities. The risk of malignant transformation of the exostoses is estimated to be up to 2%. The most common underlying cause of the disease involves mutations in either the EXT1 or the EXT2 gene. We report on the clinical and molecular findings in a family affected with HME.A mother and her three children from different partnerships, all clinically diagnosed with HME, were referred for genetic counseling. Subsequently, molecular analysis of the EXT1 gene was performed according to standard procedures. We identified a mutation in the EXT1 gene in all four affected family members (delA in codon 133). This mutation has not been previously described and is suggested to cause the disease in this family. Identification of disease causing mutations in patients with HME and their relatives can help to improve the clinical management of tumor prevention, early tumor detection, and orthopedic therapy. Show less