A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Genetics and Molecular Biology |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572021000300112 |
Resumo: | Abstract Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis. |
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Genetics and Molecular Biology |
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A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfateOsteochondromahereditaryEXT1EXT2heparan sulfateAbstract Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis.Sociedade Brasileira de Genética2021-01-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572021000300112Genetics and Molecular Biology v.44 n.2 2021reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/1678-4685-gmb-2020-0334info:eu-repo/semantics/openAccessXian,CaixiaZhu,MingweiNong,TianyingLi,YiqiangXie,XingmeiLi,XiaLi,JianguiLi,JingchunWu,JianpingShi,WeizheWei,PingXu,HongwenTang,Ya-pingeng2021-05-21T00:00:00Zoai:scielo:S1415-47572021000300112Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2021-05-21T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false |
dc.title.none.fl_str_mv |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
title |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
spellingShingle |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate Xian,Caixia Osteochondroma hereditary EXT1 EXT2 heparan sulfate |
title_short |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
title_full |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
title_fullStr |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
title_full_unstemmed |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
title_sort |
A novel mutation in ext2 caused hereditary multiple exostoses through reducing the synthesis of heparan sulfate |
author |
Xian,Caixia |
author_facet |
Xian,Caixia Zhu,Mingwei Nong,Tianying Li,Yiqiang Xie,Xingmei Li,Xia Li,Jiangui Li,Jingchun Wu,Jianping Shi,Weizhe Wei,Ping Xu,Hongwen Tang,Ya-ping |
author_role |
author |
author2 |
Zhu,Mingwei Nong,Tianying Li,Yiqiang Xie,Xingmei Li,Xia Li,Jiangui Li,Jingchun Wu,Jianping Shi,Weizhe Wei,Ping Xu,Hongwen Tang,Ya-ping |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Xian,Caixia Zhu,Mingwei Nong,Tianying Li,Yiqiang Xie,Xingmei Li,Xia Li,Jiangui Li,Jingchun Wu,Jianping Shi,Weizhe Wei,Ping Xu,Hongwen Tang,Ya-ping |
dc.subject.por.fl_str_mv |
Osteochondroma hereditary EXT1 EXT2 heparan sulfate |
topic |
Osteochondroma hereditary EXT1 EXT2 heparan sulfate |
description |
Abstract Hereditary multiple exostoses (HME) is a rare skeletal disorder characterized by the formation of multiple benign cartilage-capped tumors, usually in the metaphyseal region of the long bones. Over 70% of HME cases arise from monoallelic mutations in either of the two genes encoding the heparan sulfate (HS) synthesis enzymes, ext1 and ext2. To identify more HME-associated mutations, genomic DNA from members of five independent consanguineous families with HME was sequenced with whole exome sequencing (WES). A novel heterozygous splice site mutation (c.1173+2T>A) in ext2 was detected in all three affected members of family V. Further study showed that the novel mutation caused exon 7 of ext2 mRNA to be skipped during splicing and caused a frameshift after the codon for Arg360, which results in the appearance of new 43 codons, followed by a termination codon. Although the resulting truncated protein was still localized to the Golgi, similar to the full-length EXT2, its HS synthesis activity decreased by 40%. In this study, a novel splice site mutation in ext2 was identified and suggested to be a pathogenic mutation of HME, which may expand the genetic etiology spectrum of HME and may be helpful for clinical genetic counseling and prenatal diagnosis. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-01-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572021000300112 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572021000300112 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/1678-4685-gmb-2020-0334 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
dc.source.none.fl_str_mv |
Genetics and Molecular Biology v.44 n.2 2021 reponame:Genetics and Molecular Biology instname:Sociedade Brasileira de Genética (SBG) instacron:SBG |
instname_str |
Sociedade Brasileira de Genética (SBG) |
instacron_str |
SBG |
institution |
SBG |
reponame_str |
Genetics and Molecular Biology |
collection |
Genetics and Molecular Biology |
repository.name.fl_str_mv |
Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG) |
repository.mail.fl_str_mv |
||editor@gmb.org.br |
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1752122390488285184 |