Identification of Novel Mutations in the and Genes of Chinese Patients with Hereditary Multiple Osteochondromas.

To detect mutations in the and genes in four Chinese families with hereditary multiple osteochondromas (HMO). HMO is an autosomal dominant disorder characterized by the overgrowth of multiple cartilage-capped bones in the metaphysis of long bones and flat bones. Polymerase chain reaction-based amplification followed by DNA sequencing of the complete coding sequences of and was performed for four Chinese families with HMO. The mutant allele was found in six patients: three mutations were found in and two in . A novel frameshift mutation, which generates a premature stop codon at codon 586 and causes partial loss of the glycosyltransferase domain, was detected in exon 9 of EXT1 (F579Yfs*8). We hypothesize that F579Yfs*8 is a pathogenic mutation. Two novel missense mutations (G339S and V545D) were found in . The variant c.1634T>A (V545D) is apparently benign. In addition we found a novel deletion mutation in , c.856_864 del TTCCTCCTG, which results in the deletion of 286Phe, 287Leu, and 288Leu, that is likely pathogenic. Finally, we identified a likely benign variant in exon 13 of . c.2035-41T>C (rs3740878). We found three novel, potentially pathogenic mutations in and , including a novel frameshift mutation. More importantly, our study results have expanded the spectrum of mutations conducive to the genetic diagnosis and counseling of patients with HMO.