Mohaidat Ziyad, Bodoor Khaldon, Almomani Rowida, Alorjani Mohammed, Awwad Mohammad-Akram, Bany-Khalaf Audai, Al-Batayneh Khalid
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.
Oncol Lett. 2021 Feb;21(2):151. doi: 10.3892/ol.2020.12412. Epub 2020 Dec 30.
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.
本研究的目的是调查一部分约旦患者遗传性多发性骨软骨瘤（HMO）的分子特征，重点关注外生骨疣蛋白（EXT）1/2的基因变异及其蛋白表达。纳入了患有HMO的患者及其家庭成员。记录的临床特征包括年龄、性别、肿瘤数量和位置、关节畸形及相关功能受限情况。对EXT1和EXT2的外显子区域进行了突变分析。使用两种不同的市售兔抗人EXT1和EXT2抗体手动进行EXT1和EXT2的免疫组织化学染色。共纳入了来自9个无亲缘关系家庭的16例HMO患者，平均年龄为13.9岁。75%（12/16）的患者为男性，69%（11/16）患有轻度疾病（I级）。EXT1突变分析显示13例患者仅存在EXT1基因突变。检测到7个变异，其中3个是新变异：c.1019G>A，p.（Arg340His），c.962+1G>A和c.1469del，p.（Leu490Argfs*9）。16例患者中，3例EXT1和EXT2均未发生任何突变。免疫组织化学检查显示，所有EXT1突变患者的EXT1蛋白表达均降低。令人惊讶的是，尽管这些患者均无EXT2突变，但未检测到EXT2蛋白。大多数约旦HMO患者可能代表一个较少被研究的种族群体，多为男性，临床病程较轻；而大多数EXT1基因突变患者不一定与严重的临床病程相关。由于仅携带EXT1突变的患者未表达未突变的EXT2基因，EXT2基因的作用仍是一个有争议的话题。
