Analysis of EXT1 and EXT2 gene mutations in two Chinese pedigrees affected with hereditary multiple exostosis.
10.3760/cma.j.issn.1003-9406.2019.05.009
- VernacularTitle:两个遗传性多发性软骨瘤家系EXT1及EXT2基因的突变检测
- Author:
Ying BAI
1
;
Ning LIU
;
Shuang HU
;
Qinghua WU
;
Xiangdong KONG
Author Information
1. Center of Prenatal Diagnosis, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Email: kongxd@263.net.
- Publication Type:Journal Article
- MeSH:
DNA Mutational Analysis;
Exostoses, Multiple Hereditary;
genetics;
Female;
Humans;
Mutation;
N-Acetylglucosaminyltransferases;
genetics;
Pedigree
- From:
Chinese Journal of Medical Genetics
2019;36(5):451-455
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To detect EXT1 and EXT2 gene mutations in two pedigrees affected with hereditary multiple exostosis (HME).
METHODS:The coding regions and exon/intron boundaries of the EXT1 and EXT2 genes were analyzed by targeted next-generation sequencing (NGS). Suspected mutations were confirmed by Sanger sequencing of the probands, their family members and 200 unrelated healthy controls. Gross deletion was confirmed by quantitative PCR (qPCR) analysis and multiple ligation-dependent probe amplification (MLPA) analysis.
RESULTS:Two mutations were detected in the pedigrees, which included EXT2 gene c.337_338insG mutation in pedigree 1 and deletion of entire EXT1 in pedigree 2. Analysis of sequencing data revealed that a novel heterozygous mutation (c.337_338insG) in EXT2 gene in proband 1 and his father. The same mutation was not found among healthy family members and 200 unrelated healthy controls. As shown by NGS and MLPA analysis, proband 2 carried a heterozygous deletion of entire EXT1 gene. The same deletion was also found in her mother by qPCR.
CONCLUSION:Mutations of the EXT1 and EXT2 genes probably underlie the HME in both pedigrees. NGS combined with Sanger sequencing, qPCR and MLPA is effective for attaining the diagnosis.
