Genetic mutation analysis in three pedigrees with hereditary multiple exostosis / 中华检验医学杂志

ABSTRACT

Objective:To detect the pathogenic gene of the three pedigrees with hereditary multiple exostosis, and to provide evidences for genetic counselling and prenatal diagnosis.Methods:The three families were admitted to the Institute of Medical Genetics of Henan Provincial People′s Hospital due to hereditary multiple exostosis from January 2018 to December 2020. Detail medical history and the blood samples of the family members were collected after they signed the informed consent forms. The pathological mutations were selected from the proband using whole exome sequencing (WES). Sanger sequencing was used to conduct the co-segregation analysis of the family members. The pathogenicity of the mutation was analyzed in combination with ACMG guidelines.Results:The EXT1 gene c.1056+2T>C mutation, c.369dupA (p.G124fs) mutation and the EXT2 gene c.1171C>T (p.Q391*) mutation were detected in the probands through whole exome sequencing. The same mutations were found in the patients from these three families, while the mutation was not detected among the healthy family members. These variations have co-segregated with the disease phenotype. According to ACMG guidelines, all mutations in these three families meet the criteria of pathogenic variations. Conclusion:The EXT1 gene c.1056+2T>C mutation, c.369dupA (p.G124fs) mutation and the EXT2 gene c.1171C>T (p.Q391*) mutation were identified to be responsible for hereditary multiple exostosis in these families.