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EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis

Multiple osteochondromas (MO), the most common type of benign bone tumor, is an autosomal dominant skeletal disorder characterized by multiple cartilage-capped bony protuberances. In most cases, EXT1 and EXT2, which encode glycosyltransferases involved in the biosynthesis of heparan sulfate, are the...

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Autores principales: Wang, Ye, Zhong, Liangying, Xu, Yan, Ding, Lei, Ji, Yuanjun, Schutz, Sacha, Férec, Claude, Cooper, David N., Xu, Caixia, Chen, Jian-Min, Luo, Yanmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783290/
https://www.ncbi.nlm.nih.gov/pubmed/33414810
http://dx.doi.org/10.3389/fgene.2020.607838
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author Wang, Ye
Zhong, Liangying
Xu, Yan
Ding, Lei
Ji, Yuanjun
Schutz, Sacha
Férec, Claude
Cooper, David N.
Xu, Caixia
Chen, Jian-Min
Luo, Yanmin
author_facet Wang, Ye
Zhong, Liangying
Xu, Yan
Ding, Lei
Ji, Yuanjun
Schutz, Sacha
Férec, Claude
Cooper, David N.
Xu, Caixia
Chen, Jian-Min
Luo, Yanmin
author_sort Wang, Ye
collection PubMed
description Multiple osteochondromas (MO), the most common type of benign bone tumor, is an autosomal dominant skeletal disorder characterized by multiple cartilage-capped bony protuberances. In most cases, EXT1 and EXT2, which encode glycosyltransferases involved in the biosynthesis of heparan sulfate, are the genes responsible. Here we describe the clinical, phenotypic and genetic characterization of MO in 22 unrelated Chinese families involving a total of 60 patients. Variant detection was performed by means of a battery of different techniques including Sanger sequencing and whole-exome sequencing (WES). The pathogenicity of the missense and splicing variants was explored by means of in silico prediction algorithms. Sixteen unique pathogenic variants, including 10 in the EXT1 gene and 6 in the EXT2 gene, were identified in 18 (82%) of the 22 families. Fourteen (88%) of the 16 variants were predicted to give rise to truncated proteins whereas the remaining two were missense. Seven variants were newly described here, further expanding the spectrum of MO-causing variants in the EXT1 and EXT2 genes. More importantly, the identification of causative variants allowed us to provide genetic counseling to 8 MO patients in terms either of preimplantation genetic testing (PGT) or prenatal diagnosis, thereby preventing the reoccurrence of MO in the corresponding families. This study is the first to report the successful implementation of PGT in MO families and describes the largest number of subjects undergoing prenatal diagnosis to date.
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spelling pubmed-77832902021-01-06 EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis Wang, Ye Zhong, Liangying Xu, Yan Ding, Lei Ji, Yuanjun Schutz, Sacha Férec, Claude Cooper, David N. Xu, Caixia Chen, Jian-Min Luo, Yanmin Front Genet Genetics Multiple osteochondromas (MO), the most common type of benign bone tumor, is an autosomal dominant skeletal disorder characterized by multiple cartilage-capped bony protuberances. In most cases, EXT1 and EXT2, which encode glycosyltransferases involved in the biosynthesis of heparan sulfate, are the genes responsible. Here we describe the clinical, phenotypic and genetic characterization of MO in 22 unrelated Chinese families involving a total of 60 patients. Variant detection was performed by means of a battery of different techniques including Sanger sequencing and whole-exome sequencing (WES). The pathogenicity of the missense and splicing variants was explored by means of in silico prediction algorithms. Sixteen unique pathogenic variants, including 10 in the EXT1 gene and 6 in the EXT2 gene, were identified in 18 (82%) of the 22 families. Fourteen (88%) of the 16 variants were predicted to give rise to truncated proteins whereas the remaining two were missense. Seven variants were newly described here, further expanding the spectrum of MO-causing variants in the EXT1 and EXT2 genes. More importantly, the identification of causative variants allowed us to provide genetic counseling to 8 MO patients in terms either of preimplantation genetic testing (PGT) or prenatal diagnosis, thereby preventing the reoccurrence of MO in the corresponding families. This study is the first to report the successful implementation of PGT in MO families and describes the largest number of subjects undergoing prenatal diagnosis to date. Frontiers Media S.A. 2020-12-22 /pmc/articles/PMC7783290/ /pubmed/33414810 http://dx.doi.org/10.3389/fgene.2020.607838 Text en Copyright © 2020 Wang, Zhong, Xu, Ding, Ji, Schutz, Férec, Cooper, Xu, Chen and Luo. http://creativecommons.org/licenses/by/4.0/ 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) and the copyright owner(s) 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.
spellingShingle Genetics
Wang, Ye
Zhong, Liangying
Xu, Yan
Ding, Lei
Ji, Yuanjun
Schutz, Sacha
Férec, Claude
Cooper, David N.
Xu, Caixia
Chen, Jian-Min
Luo, Yanmin
EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
title EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
title_full EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
title_fullStr EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
title_full_unstemmed EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
title_short EXT1 and EXT2 Variants in 22 Chinese Families With Multiple Osteochondromas: Seven New Variants and Potentiation of Preimplantation Genetic Testing and Prenatal Diagnosis
title_sort ext1 and ext2 variants in 22 chinese families with multiple osteochondromas: seven new variants and potentiation of preimplantation genetic testing and prenatal diagnosis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783290/
https://www.ncbi.nlm.nih.gov/pubmed/33414810
http://dx.doi.org/10.3389/fgene.2020.607838
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