Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.

Multiple osteochondromas (MO) is an inherited skeletal disorder, and the molecular mechanism of MO remains elusive. Exome sequencing has high chromosomal coverage and accuracy, and has recently been successfully used to identify pathogenic gene mutations. In this study, exome sequencing followed by...

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Autores principales:	Feng Zhang, Jinlong Liang, Xiong Guo, Yingang Zhang, Yan Wen, Qiang Li, Zengtie Zhang, Weijuan Ma, Lanlan Dai, Xuanzhu Liu, Ling Yang, Jun Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f2a1b3303cbd4e3b800f2d2c925e4aba
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spelling	oai:doaj.org-article:f2a1b3303cbd4e3b800f2d2c925e4aba2021-11-18T08:57:46ZExome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.1932-620310.1371/journal.pone.0072316https://doaj.org/article/f2a1b3303cbd4e3b800f2d2c925e4aba2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24009674/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple osteochondromas (MO) is an inherited skeletal disorder, and the molecular mechanism of MO remains elusive. Exome sequencing has high chromosomal coverage and accuracy, and has recently been successfully used to identify pathogenic gene mutations. In this study, exome sequencing followed by Sanger sequencing validation was first used to screen gene mutations in two representative MO patients from a Chinese family. After filtering the data from the 1000 Genome Project and the dbSNP database (build 132), the detected candidate gene mutations were further validated via Sanger sequencing of four other members of the same MO family and 200 unrelated healthy subjects. Immunohistochemisty and multiple sequence alignment were performed to evaluate the importance of the identified causal mutation. A novel frameshift mutation, c.1457insG at codon 486 of exon 6 of EXT1 gene, was identified, which truncated the glycosyltransferase domain of EXT1 gene. Multiple sequence alignment showed that codon 486 of EXT1 gene was highly conserved across various vertebrates. Immunohistochemisty demonstrated that the chondrocytes with functional EXT1 in MO were less than those in extragenetic solitary chondromas. The novel c.1457insG deleterious mutation of EXT1 gene reported in this study expands the causal mutation spectrum of MO, and may be helpful for prenatal genetic screening and early diagnosis of MO.Feng ZhangJinlong LiangXiong GuoYingang ZhangYan WenQiang LiZengtie ZhangWeijuan MaLanlan DaiXuanzhu LiuLing YangJun WangJun WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72316 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Feng Zhang Jinlong Liang Xiong Guo Yingang Zhang Yan Wen Qiang Li Zengtie Zhang Weijuan Ma Lanlan Dai Xuanzhu Liu Ling Yang Jun Wang Jun Wang Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.
description	Multiple osteochondromas (MO) is an inherited skeletal disorder, and the molecular mechanism of MO remains elusive. Exome sequencing has high chromosomal coverage and accuracy, and has recently been successfully used to identify pathogenic gene mutations. In this study, exome sequencing followed by Sanger sequencing validation was first used to screen gene mutations in two representative MO patients from a Chinese family. After filtering the data from the 1000 Genome Project and the dbSNP database (build 132), the detected candidate gene mutations were further validated via Sanger sequencing of four other members of the same MO family and 200 unrelated healthy subjects. Immunohistochemisty and multiple sequence alignment were performed to evaluate the importance of the identified causal mutation. A novel frameshift mutation, c.1457insG at codon 486 of exon 6 of EXT1 gene, was identified, which truncated the glycosyltransferase domain of EXT1 gene. Multiple sequence alignment showed that codon 486 of EXT1 gene was highly conserved across various vertebrates. Immunohistochemisty demonstrated that the chondrocytes with functional EXT1 in MO were less than those in extragenetic solitary chondromas. The novel c.1457insG deleterious mutation of EXT1 gene reported in this study expands the causal mutation spectrum of MO, and may be helpful for prenatal genetic screening and early diagnosis of MO.
format	article
author	Feng Zhang Jinlong Liang Xiong Guo Yingang Zhang Yan Wen Qiang Li Zengtie Zhang Weijuan Ma Lanlan Dai Xuanzhu Liu Ling Yang Jun Wang Jun Wang
author_facet	Feng Zhang Jinlong Liang Xiong Guo Yingang Zhang Yan Wen Qiang Li Zengtie Zhang Weijuan Ma Lanlan Dai Xuanzhu Liu Ling Yang Jun Wang Jun Wang
author_sort	Feng Zhang
title	Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.
title_short	Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.
title_full	Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.
title_fullStr	Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.
title_full_unstemmed	Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.
title_sort	exome sequencing and functional analysis identifies a novel mutation in ext1 gene that causes multiple osteochondromas.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f2a1b3303cbd4e3b800f2d2c925e4aba
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Exome sequencing and functional analysis identifies a novel mutation in EXT1 gene that causes multiple osteochondromas.

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