Identification of Novel EXT Mutations in Patients with Hereditary Multiple Exostoses Using Whole‐Exome Sequencing

• DOI: 10.1111/os.12660
• Publication Date: 2020-04-15T14:40:44Z
• Authors: Chao Liang; Yong‐jie Wang; Yu‐xuan Wei; Yang Dong; Zhi‐chang Zhang
• Keywords: Sanger sequencing; Hereditary multiple exostoses

Objective To find novel potential gene mutations other than EXT1 and EXT2 mutations, to expand the mutational spectrum of EXT explore correlation between clinical outcome genotype in patients with hereditary multiple exostoses (HME). Methods The study recruited seven families diagnosed osteochondromas (MO). Family histories information were collected detail through comprehensive physical image examination. Patients deformities functional limitations classified as “severe” remaining without “mild,” accordance previous study. Whole‐exome sequencing (WES) was performed on a total 13 affected individuals, 1 available unaffected relative, 10 healthy unrelated individuals. Sanger used validate screened mutations. Finally, structural change protein caused by pathogenic analyzed using from relevant database online we attempted correlate phenotype HME. Results Other EXT2, no found WES. We identified nine heterozygous or EXT2. Of these four have not been reported previously. These are c.996delT exon 2 (family 1), c.544C > T 3 2), c.1171C 7 5), c.823 – 824delAA 5 7). five already works. It surprising that two mutation sites, 5, respectively, patient MO, when his father had 6 4). In addition, showed degeneration, while only exhibited slight symptoms our study, among 51 families, sex ratio (male vs female) 58.9% ( n = 30) 41.2% 21). Male seemed show more severe compared females, but because sample small, did obtain statistically significance results. Conclusion screen applied successfully. Although third‐gene associated HME found, across identified, which novel. Our results can be genetic counseling prenatal diagnosis for MO.