Identification of Novel Mutations in the EXT1 and EXT2 Genes of Chinese Patients with Hereditary Multiple Osteochondromas

• Published in: Genetic testing and molecular biomarkers Vol. 25; no. 2; p. 145
• Main Authors: Tong, Yu, Zhang, Yin, Luo, Junchao, Hong, Zheping, Chen, Xinji, Bi, Qing
• Format: Journal Article
• Language: English
• Published: United States 01.02.2021
• Subjects: hereditary multiple osteochondromas; exostosin glycosyltransferase 2; frameshift mutation; exostosin glycosyltransferase 1; hereditary multiple exostoses
• ISSN: 1945-0257
• DOI: 10.1089/gtmb.2020.0098

To detect mutations in the and genes in four Chinese families with hereditary multiple osteochondromas (HMO). HMO is an autosomal dominant disorder characterized by the overgrowth of multiple cartilage-capped bones in the metaphysis of long bones and flat bones. Polymerase chain reaction-based amplification followed by DNA sequencing of the complete coding sequences of and was performed for four Chinese families with HMO. The mutant allele was found in six patients: three mutations were found in and two in . A novel frameshift mutation, which generates a premature stop codon at codon 586 and causes partial loss of the glycosyltransferase domain, was detected in exon 9 of EXT1 (F579Yfs*8). We hypothesize that F579Yfs*8 is a pathogenic mutation. Two novel missense mutations (G339S and V545D) were found in . The variant c.1634T>A (V545D) is apparently benign. In addition we found a novel deletion mutation in , c.856_864 del TTCCTCCTG, which results in the deletion of 286Phe, 287Leu, and 288Leu, that is likely pathogenic. Finally, we identified a likely benign variant in exon 13 of . c.2035-41T>C (rs3740878). We found three novel, potentially pathogenic mutations in and , including a novel frameshift mutation. More importantly, our study results have expanded the spectrum of mutations conducive to the genetic diagnosis and counseling of patients with HMO.