Novel EXT1 mutation identified in a pedigree with hereditary multiple exostoses

Cao,Li; Liu,Fei; Kong,Mingxiang; Fang,Yong; Gu,Haifeng; Chen,Yu; Zhao,Chen; Zhang,Shuijun; Bi,Qing

doi:10.3892/or.2013.2891

Novel EXT1 mutation identified in a pedigree with hereditary multiple exostoses

Authors:
- Li Cao
- Fei Liu
- Mingxiang Kong
- Yong Fang
- Haifeng Gu
- Yu Chen
- Chen Zhao
- Shuijun Zhang
- Qing Bi
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Affiliations: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China, Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Institute of Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, P.R. China
Published online on: December 2, 2013 https://doi.org/10.3892/or.2013.2891
Pages: 713-718

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Abstract

Hereditary multiple exostoses (HME) is an autosomal dominant bone disorder characterized by the presence of multiple benign cartilage-capped tumors. EXT1 located on chromosome 8q23-q24 and EXT2 located on 11p11-p12 are the main disease-causing genes which are responsible for ~90% of HME cases. Mutations of EXT1 or EXT2 result in insufficient heparan sulfate biosynthesis, which facilitates chondrocyte proliferation, boosts abnormal bone growth of neighboring regions, causes multiple exostoses, and ultimately leads to possible malignant transformation. A family who displayed typical features of HME was enrolled in the present study. Mutation screening by Sanger sequencing identified a novel heterozygous nonsense mutation c.1902C>A (p.Tyr634X) in the EXT1 gene exclusively in all 3 patients, which is located in the glycosyltransferase domain and results in the truncation of 112 amino acids at the C-terminus of the EXT1 protein. Thus, the present study identified a novel disease-causing EXT1 mutation in a pedigree with HME, which provides additional evidence for developing quick and accurate genetic tools for HME diagnosis.

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