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 was used to examine the entire coding regions of EXT(1) gene on chromosome 8 and EXT(2) 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 EXT(1) gene, and the other was the deletion of four bases (tgtt) in exon 2 of the EXT(2) gene. Both of the mutations resulted in a frameshift and premature termination of translation.

Conclusions: 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 counseling and prenatal genetic diagnosis of EXT.