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Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses
BACKGROUND: Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905910/ https://www.ncbi.nlm.nih.gov/pubmed/33632255 http://dx.doi.org/10.1186/s13023-021-01738-z |
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author | Al-Zayed, Zayed Al-Rijjal, Roua A. Al-Ghofaili, Lamya BinEssa, Huda A. Pant, Rajeev Alrabiah, Anwar Al-Hussainan, Thamer Zou, Minjing Meyer, Brian F. Shi, Yufei |
author_facet | Al-Zayed, Zayed Al-Rijjal, Roua A. Al-Ghofaili, Lamya BinEssa, Huda A. Pant, Rajeev Alrabiah, Anwar Al-Hussainan, Thamer Zou, Minjing Meyer, Brian F. Shi, Yufei |
author_sort | Al-Zayed, Zayed |
collection | PubMed |
description | BACKGROUND: Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase 2 (EXT2). The genetic defects have not been studied in the Saudi patients. AIM OF STUDY: We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families. METHODS: Genomic DNA was extracted from peripheral leucocytes. The coding regions and intron–exon boundaries of both EXT1 and EXT2 genes were screened for mutations by PCR-sequencing analysis. Gross deletions were analyzed by MLPA analysis. RESULTS: EXT1 mutations were detected in 6 families (35%) and 3 were novel mutations: c.739G > T (p. E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25). EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1. Five patients from different families had no family history and carried de novo mutations (29%, 5/17). No EXT1 and EXT2 mutations were found in the remaining four families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients. CONCLUSION: EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients. De novo mutations are also common and the six novel EXT1/EXT2 mutations further expands the mutation spectrum of HME. |
format | Online Article Text |
id | pubmed-7905910 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79059102021-02-26 Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses Al-Zayed, Zayed Al-Rijjal, Roua A. Al-Ghofaili, Lamya BinEssa, Huda A. Pant, Rajeev Alrabiah, Anwar Al-Hussainan, Thamer Zou, Minjing Meyer, Brian F. Shi, Yufei Orphanet J Rare Dis Research BACKGROUND: Hereditary Multiple Exostoses (HME), also known as Multiple Osteochondromas (MO) is a rare genetic disorder characterized by multiple benign cartilaginous bone tumors, which are caused by mutations in the genes for exostosin glycosyltransferase 1 (EXT1) and exostosin glycosyltransferase 2 (EXT2). The genetic defects have not been studied in the Saudi patients. AIM OF STUDY: We investigated mutation spectrum of EXT1 and EXT2 in 22 patients from 17 unrelated families. METHODS: Genomic DNA was extracted from peripheral leucocytes. The coding regions and intron–exon boundaries of both EXT1 and EXT2 genes were screened for mutations by PCR-sequencing analysis. Gross deletions were analyzed by MLPA analysis. RESULTS: EXT1 mutations were detected in 6 families (35%) and 3 were novel mutations: c.739G > T (p. E247*), c.1319delG (p.R440Lfs*4), and c.1786delA (p.S596Afs*25). EXT2 mutations were detected in 7 families (41%) and 3 were novel mutations: c.541delG (p.D181Ifs*89), c.583delG (p.G195Vfs*75), and a gross deletion of approximately 10 kb including promoter and exon 1. Five patients from different families had no family history and carried de novo mutations (29%, 5/17). No EXT1 and EXT2 mutations were found in the remaining four families. In total, EXT1 and EXT2 mutations were found in 77% (13/17) of Saudi HME patients. CONCLUSION: EXT1 and EXT2 mutations contribute significantly to the pathogenesis of HME in the Saudi population. In contrast to high mutation rate in EXT 1 (65%) and low mutation rate in EXT2 (25%) in other populations, the frequency of EXT2 mutations are much higher (41%) and comparable to that of EXT1 among Saudi patients. De novo mutations are also common and the six novel EXT1/EXT2 mutations further expands the mutation spectrum of HME. BioMed Central 2021-02-25 /pmc/articles/PMC7905910/ /pubmed/33632255 http://dx.doi.org/10.1186/s13023-021-01738-z Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Al-Zayed, Zayed Al-Rijjal, Roua A. Al-Ghofaili, Lamya BinEssa, Huda A. Pant, Rajeev Alrabiah, Anwar Al-Hussainan, Thamer Zou, Minjing Meyer, Brian F. Shi, Yufei Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses |
title | Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses |
title_full | Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses |
title_fullStr | Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses |
title_full_unstemmed | Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses |
title_short | Mutation spectrum of EXT1 and EXT2 in the Saudi patients with hereditary multiple exostoses |
title_sort | mutation spectrum of ext1 and ext2 in the saudi patients with hereditary multiple exostoses |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905910/ https://www.ncbi.nlm.nih.gov/pubmed/33632255 http://dx.doi.org/10.1186/s13023-021-01738-z |
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