Skip to main content

CASE REPORT article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1435493

Cases Report: Mosaic structural variants of EXT1 gene in previously genetically unconfirmed multiple osteochondromas

Provisionally accepted
Artem Borovikov Artem Borovikov 1*Andrey Marakhonov Andrey Marakhonov 1Aysylu Murtazina Aysylu Murtazina 1Kseniya Davydenko Kseniya Davydenko 1ALEXANDRA FILATOVA ALEXANDRA FILATOVA 1Nailya Galeeva Nailya Galeeva 1Varvara Kadnikova Varvara Kadnikova 1Natalya Ogorodova Natalya Ogorodova 1Daria Gorodilova Daria Gorodilova 1Ilya Kanivets Ilya Kanivets 2,3Denis Pyankov Denis Pyankov 2Konstantin Zherdev Konstantin Zherdev 4,5Aleksandr Petel'guzov Aleksandr Petel'guzov 4Pavel Zubkov Pavel Zubkov 4Alexander Polyakov Alexander Polyakov 1Olga Shchagina Olga Shchagina 1Mikhail Skoblov Mikhail Skoblov 1
  • 1 Research Centre for Medical Genetics, Moscow, Russia
  • 2 Genomed Ltd., Moscow, Moscow Oblast, Russia
  • 3 Other, Moscow, Russia
  • 4 National Medical Research Center for Children's Health, Ministry of Health of the Russian Federation, Moscow, Moscow Oblast, Russia
  • 5 I.M. Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia

The final, formatted version of the article will be published soon.

    Multiple osteochondromas (MO) is a rare autosomal dominant skeletal disorder characterized by the development of multiple benign tumors known as osteochondromas. The condition is predominantly caused by loss-of-function variants in the EXT1 or EXT2 genes, facilitating relatively precise clinical diagnosis through established diagnostic criteria. Despite this, a notable percentage of MO cases (10-20%) remain unresolved after sequencing coding regions and copy number analysis of both genes.In our study, we identified mosaic structural variants in two patients initially yielding negative results on standard genetic analysis for MO. Specifically, mosaic deletions affecting exon 8-11 and exon 2-11 in the EXT1 gene were detected. RNA analysis was performed in one case, while both cases underwent genome sequencing. To date, only six mosaic copy number variations have been reported in association with MO, representing a minority among known variants in both genes.Our report provides a detailed analysis of these findings, highlighting the significance of advanced genetic testing techniques in detecting mosaic variants in the EXT1/2 genes.

    Keywords: Multiple osteochondromas, Exostosis, EXT1, EXT2, mosaic deletion, Genome sequencing

    Received: 20 May 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Borovikov, Marakhonov, Murtazina, Davydenko, FILATOVA, Galeeva, Kadnikova, Ogorodova, Gorodilova, Kanivets, Pyankov, Zherdev, Petel'guzov, Zubkov, Polyakov, Shchagina and Skoblov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Artem Borovikov, Research Centre for Medical Genetics, Moscow, Russia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.