title: Novel EXT1 mutation identified in a pedigree with hereditary multiple exostoses.
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.
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Mingxiang
authors.initials: M
authors.lastname: Kong
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics and Joint Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Bi
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D018389:Codon, Nonsense / Q000235:genetics; D005097:Exostoses, Multiple Hereditary / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D000099065:Exostosin 2; D000099058:Exostosin 1
chemical_list: D018389:Codon, Nonsense; D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; D000099065:Exostosin 2