Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma

Xia,Peng; Xu,Haikun; Shi,Qingyang; Li,Dejun

doi:10.3892/ol.2015.3844

Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma

Authors:
- Peng Xia
- Haikun Xu
- Qingyang Shi
- Dejun Li
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Affiliations: Department of Spinal Surgery, Orthopedics Hospital, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Cardiology, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Center for Prenatal Diagnosis, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: October 29, 2015 https://doi.org/10.3892/ol.2015.3844
Pages: 105-110
Copyright: © Xia et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple osteochondroma (MO), also known as multiple hereditary exostoses, is an autosomal dominant skeletal disorder with characteristic multiple cartilage‑capped tumours (osteochondromas or exostoses) growing outward from the metaphyseal region of the long tubular bones. Mutations in exostosin glycosyltransferase 1 (EXT1) or EXT2 are the most commonly associated mutations with MO and are responsible for 70‑95% of cases. In the present study, a genetic analysis was performed on a large family with MO using polymerase chain reaction and direct DNA sequencing of the entire coding regions of EXT1 and EXT2. Sanger sequencing identified a novel heterozygous frameshift mutation, c.119_120delCT (p.Thr40ArgfsX15), in exon 2 of the EXT2 gene in the proband and all other affected individuals, while this deleterious mutation was not detected in the healthy family members and normal controls. The c.119_120delCT mutation is located in the transmembrane region of the EXT2 protein and results in a truncated EXT2 protein lacking 665 amino acids at the C‑terminus, which includes the critical exostosin and glycosyltransferase family 64 domains. Thus, the present study identified a novel causative frameshift mutation in EXT2 from a large MO family. This study is useful for extending the known mutational spectrum of EXT2, for understanding the genetic basis of MO in the patients studied, and for further application of mutation screening in the genetic counseling and subsequent prenatal diagnosis of this family.

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