+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

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

Plos one 8(8): E72316

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053120911

Download citation: RISBibTeXText

PMID: 24009674

DOI: 10.1371/journal.pone.0072316

Related references

Identification of a novel mutation in the EXT1 gene from a patient with multiple osteochondromas by exome sequencing. Molecular Medicine Reports 15(2): 657-664, 2017

Mutation analysis and prenatal diagnosis of EXT1 gene mutations in Chinese patients with multiple osteochondromas. Chinese Medical Journal 124(19): 3054-3057, 2011

Identification of a novel EXT1 mutation in patients with hereditary multiple exostosis by exome sequencing. Oncology Reports 33(2): 547-552, 2015

Mutation screening of EXT1 and EXT2 by denaturing high-performance liquid chromatography, direct sequencing analysis, fluorescence in situ hybridization, and a new multiplex ligation-dependent probe amplification probe set in patients with multiple osteochondromas. Journal of Molecular Diagnostics 10(1): 85-92, 2008

Exome sequencing and functional analysis identifies BANF1 mutation as the cause of a hereditary progeroid syndrome. American Journal of Human Genetics 88(5): 650-656, 2011

A Novel EXT1 Mutation Identified in a Family with Multiple Osteochondromas. Genetic Testing and Molecular Biomarkers 23(4): 251-254, 2019

Mutation screening for the EXT1 and EXT2 genes in Chinese patients with multiple osteochondromas. Archives of Medical Research 44(7): 542-548, 2013

Whole-exome sequencing identifies a novel homozygous frameshift mutation in the PROM1 gene as a causative mutation in two patients with sporadic retinitis pigmentosa. International Journal of Molecular Medicine 37(6): 1528-1534, 2016

RNA-Seq detects a SAMD12-EXT1 fusion transcript and leads to the discovery of an EXT1 deletion in a child with multiple osteochondromas. Molecular Genetics and Genomic Medicine 7(3): E00560, 2019

Whole-Exome Sequencing Identifies a Novel Homozygous Frameshift Mutation in the MTMR2 Gene as a Causative Mutation in a Patient with Charcot-Marie-Tooth Disease Type 4B1. Molecular Neurobiology 55(4): 3546-3550, 2018

Mutation screening of EXT1 and EXT2 by direct sequence analysis and MLPA in patients with multiple osteochondromas: splice site mutations and exonic deletions account for more than half of the mutations. European Journal of Human Genetics 13(4): 470-474, 2005

Exome capture sequencing identifies a novel CCM1 mutation in a Chinese family with multiple cerebral cavernous malformations. International Journal of Neuroscience 126(12): 1071-1076, 2016

Whole exome sequencing identifies a novel mutation in the transglutaminase 6 gene for spinocerebellar ataxia in a Chinese family. Clinical Genetics 83(3): 269-273, 2013

Whole exome sequencing identifies a novel frameshift mutation in GPC3 gene in a patient with overgrowth syndrome. Gene 572(2): 303-306, 2015

Whole Exome Sequencing Identifies a Novel and a Recurrent Mutation in BBS2 Gene in a Family with Bardet-Biedl Syndrome. Biomed Research International 2015: 524754, 2015