Germline mutations in the EXT1 and EXT2 genes in Korean patients with hereditary multiple exostoses

Hereditary multiple exostoses (EXT) is an autosomal dominantly inherited di sease characterized by the formation of cartilage-capped prominences (exost oses) that develop from the juxtaepiphyseal regions of the long bones. Rece ntly, EXT1 and EXT2 genes were cloned and germline mutations of EXT1 and EX T2 were identified in EXT families, In this study, we performed a mutationa l analysis of EXT1 and EXT2 genes in eight unrelated Korean EXT families by polymerase chain reaction (PCR)-single strand conformation polymorphism (S SCP) analysis followed by direct DNA sequencing. As a result, we were able to identify one family (SNU-OC3) with the EXT1 mutation and another family (SNU-OC15) with the EXT2 mutation. The EXT1 mutation was a 10-bp deletion a t the 3' end of exon 5 (CTAATTTAGg) including the splice site of this exon. The EXT2 mutation identified in the SNU-OC15 family was a missense mutatio n at codon 85 of exon 2 (TGC --> CGC), resulting in an amino acid change fr om cysteine to arginine. This missense mutation cosegregated with the disea se phenotype in this family, suggesting that it is the disease-causing muta tion. These two mutations identified in EXT1 and EXT2 are novel ones.