Hereditary multiple osteochondromas in Jordanian patients: Mutational and immunohistochemical analysis of <em>EXT1</em> and <em>EXT2</em> genes

Mohaidat,Ziyad; Bodoor,Khaldon; Almomani,Rowida; Alorjani,Mohammed; Awwad,Mohammad-Akram; Bany‑Khalaf,Audai; Al‑Batayneh,Khalid

doi:10.3892/ol.2020.12412

Hereditary multiple osteochondromas in Jordanian patients: Mutational and immunohistochemical analysis of EXT1 and EXT2 genes

Authors:
- Ziyad Mohaidat
- Khaldon Bodoor
- Rowida Almomani
- Mohammed Alorjani
- Mohammad-Akram Awwad
- Audai Bany‑Khalaf
- Khalid Al‑Batayneh
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Affiliations: Orthopedic Division, Special Surgery Department, Faculty of Medicine, Jordan University of Science and Technology, King Abdullah University Hospital, Irbid 22110, Jordan, Department of Applied Biology, Faculty of Science, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Laboratory Medical Sciences, Faculty of Science, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Pathology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Clinical Sciences, Faculty of Medicine, Yarmouk University, Irbid 21110, Jordan, Orthopedic Division, Special Surgery Department, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan, Department of Biology, Faculty of Sciences, Yarmouk University, Irbid 21110, Jordan
Published online on: December 30, 2020 https://doi.org/10.3892/ol.2020.12412
Article Number: 151
Copyright: © Mohaidat et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 (EXT1)/(EXT2) 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 EXT1 and EXT2 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). EXT mutation analysis revealed only EXT1 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 EXT1 or EXT2. Immunohistochemical examination revealed decreased expression of EXT1 protein in all patients with EXT1 mutation. Surprisingly, EXT2 protein was not detected in these patients, although none had EXT2 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 EXT1 gene mutations were not necessarily associated with a severe clinical disease course. The role of EXT2 gene remains a subject of debate, since patients with EXT1 mutations alone did not express the non‑mutated EXT2 gene.

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