Van gen naar ziekte; hereditaire multipele exostosen

Hereditary multiple exostoses is an autosomal dominant disorder characterised by the presence of multiple osteochondromas, resulting in a variety of skeletal deformities. It is a genetically heterogeneous condition for which two genes, EXT1 and EXT2, have been isolated. The EXT1 gene, located at 8q24, has been shown to harbour mutations in 44-66% of the hereditary multiple exostoses-families. Mutations in the EXT2 gene, located at 11p11-p12, are detected in about 30% of the families. Additional linkage to chromosome 19p suggests the existence of an EXT3 gene. EXT1 has been shown to act as a tumour suppressor gene in hereditary multiple exostoses, resulting in osteochondroma formation when both copies of EXT1 are lost. Diagnostic germ-line mutation analysis is operative in the Clinical Genetic Center Leiden, the Netherlands.