Structural Aberrations in the EXT1 and EXT2 Genes: New Cases of Hereditary Multiple Osteochondromas and Population...

Hereditary multiple osteochondromas is an autosomal dominant disease associated with mutations of the exostosin gene family. Phenotypically, it is manifested as a skeletal dysplasia. The growth of multiple osteochondromas, cartilaginous bone nodules in the diaphysis area, can change into benign cartilaginous bone tumors which overgrow outside the metaphysis of the long bones. The aim of this study was to (1) verify the role of structural aberrations in the EXT1 and EXT2 genes, and (2) confront the findings with structural variants found in the general population. This study can thus contribute to understanding the etiology of HMO.

In this article, we describe a group of 8 patients with hereditary multiple osteochondromas and a control group of 120 healthy individuals whose DNA was analyzed using the MLPA method to detect structural changes.

Some structural aberrations were found in 4 from 6 probands (6 from 8 all patients respectively) and in 3 from 120 healthy individuals (2.5%). Structural aberrations appear to be a significant defect in the EXT1 and EXT2 genes, and their role in etiopathogenesis is therefore crucial, consistent with published work. The issue of aberrations in healthy individuals is less clear. It is worth noting that while published work in patients and healthy individuals describes deletions, this study also revealed duplication.

The actual occurrence, especially the significance of structural variants in the EXT1 and EXT2 genes, is uncertain and remains the subject of further investigations.