Identification of mutations in the human EXT₁ and EXT₂ genes

Objective: To investigate further the genetic basis of hereditary multiple exostoses (EXT) and provide useful information for gene diagnosis of the disease. Methods: Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) was used to examine the entire coding regions of EXT₁ gene on chromosome 8 and EXT₂ gene on chromosome 11 for mutation in thirty EXT families. Mutations were further identified by sequencing. Results: Two frameshift mutations were identified in two unrelated EXT families. One was the deletion of one base(T) in exon 6 of the EXT₁ gene, and the other was the deletion of four bases (tgtt) in exon 2 of the EXT₂ gene. Both of the mutations resulted in a frameshift and premature termination of translation. Conclusion: EXT is a genetically heterogeneous bone disorder caused by the mutation of EXT tumor suppressor gene. These results could be directly applied in the genetic counselling and prenatal genetic diagnosis of EXT.