Research On The Pathogenic Genes And Mechanisms Of Hereditary Multiple Exostoses

OBJECTIVEHereditary multiple exostoses is an autosomal dominant hereditary bone disease characterized by familial onset and characterized by bone tumors covered with cartilage caps.The disease is mainly associated with mutations in the tumor suppressor gene Exostosin-1(EXT1)or Exostosin-2(EXT2)of the EXT gene family.In this study,we will conduct an in-depth investigation on a family of hereditary multiple exostoses with multiple patients.Method1.Drawing the pedigree of the family through in-depth communication with the proband.After obtaining the consent,the family members of the family were visited for physical examination and peripheral blood samples were taken.A more detailed physical examination,imaging examination and blood examination for two members who had undergone malignant transformation.After confirming the condition of 2 patients,the 2malignant patients were operated operation for 3 times,and the tumor specimens were retained after the operation.2.The consent of the patient and his family was used to perform genome-wide sequencing of the tumor specimens and blood specimens of the branch family.3.Blood samples were taken from the other 12 members of the family,DNA was extracted,and each exon of EXT2 and HOGA1 was amplified by polymerase chain reaction,and the obtained product was detected.Results:1.After a detailed survey of the family,we mapped the pedigree of the family.According to the pedigree,we know that there are a total of 29 people in the family.One person died a normal old age with tumors.There are 28 people in existence,and 7 of them are patients.There are four branches in the family,and there exists patients in the two branches.One of the families has frequent malignant tumors.We detected two pathogenic mutations in the genome-wide test of 8 samples from 6 members of the malignant branch family: EXT2 mutation and HOGA1 mutation.The proband's father has a 3 base deletion mutation in the exon of the EXT2 gene: c.824-826 delGCA,the proband's mother(normal member)has a missense mutation in the exon of the HOGA1gene: c.715G>A|p.Val239 Ile.2.Among the other 12 members,only the EXT2 gene mutation was present in thepatients,and the normal members had no obvious pathogenic mutations.Conclusion:1.This family is indeed a family of hereditary multiple exostoses,and the clinical manifestations vary greatly among several branch families of this family.2.The cause of hereditary multiple osteochondroma is EXT2 gene mutation,and the cause of malignant transformation may be caused by mutation of HOGA1 gene.3.The cause of malignant transformation of the tumor is the HOGA1 gene mutation.