Objective: To identify the gene causing hereditary multiple exostoses in a Chinese pedigree.

Methods: Linkage analysis was carried out in the family using microsatellite markers on chromosome 8, 11 and 19 respectively. To detect the mutation, the whole coding sequence and the intron-exon boundaries of the candidate gene were amplified and sequenced. The reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the mutated mRNA.

Results: The disease-causing gene of the family was linked to the EXT2 locus on chromosome 11. A mutation IVS2+1G>A was detected in EXT2 and resulting in 221 bp deletion from 316 to 536 of coding sequence(CDS), which was co-segregated with the disease phenotype. This change led to deletion from codon 106 to codon 178 and subsequent 2 nucleotides, producing a frameshift and truncated protein of 125 aa.

Conclusions: The mutation IVS2+1G>A is the disease-causing mutation in the Chinese pedigree with hereditary multiple exostoses.