Hereditary multiple osteochondromas in Jordanian patients: Mutational and immunohistochemical analysis of and genes.

The aim of the present study was to investigate the molecular characteristics of hereditary multiple osteochondromas (HMO) in a subset of Jordanian patients with a focus on the genetic variants of exostosin ()/() and their protein expression. Patients with HMO and their family members were included. Recorded clinical characteristics included age, sex, tumors number and location, joint deformities and associated functional limitations. Mutational analysis of and exonic regions was performed. Immunohistochemical staining for EXT1 and EXT2 was performed manually using two different commercially available rabbit anti-human EXT1 and EXT2 antibodies. A total of 16 patients with HMO from nine unrelated families were included, with a mean age of 13.9 years. A total of 75% (12/16) of the patients were male and (69%) (11/16) had a mild disease (class I). mutation analysis revealed only gene mutations in 13 patients. Seven variants were detected, among which three were novel: c.1019G>A, p. (Arg340His), c.962+1G>A and c.1469del, p. (Leu490Argfs*9). Of the 16 patients, 3 did not harbor any mutations for either or . Immunohistochemical examination revealed decreased expression of EXT1 protein in all patients with mutation. Surprisingly, EXT2 protein was not detected in these patients, although none had mutations. The majority of Jordanian patients with HMO, who may represent an ethnic group that is infrequently investigated, were males and had a mild clinical disease course; whereas most patients with gene mutations were not necessarily associated with a severe clinical disease course. The role of gene remains a subject of debate, since patients with mutations alone did not express the non-mutated gene.