Mutation Screening Of EXT Genes In A Famlily With Hereditary Multiple Exostoses

Objective: In order to identify the causative mutation in the pedigree with hereditary multiple exostoses(HME),we collect the clinical data and detect all coding sequences of EXT1 and EXT2 gene of all members in this pedigree.This study can provide molecular genetic basis for the mechanism research of HME,also effective theoretical basis for genetic counseling and prenatal diagnosis in this family.Methods: A questionnaire survey was conducted on a three-generation famliy with HME from zhejiang province,and the family pedigree with HME was drawn.Then,the detailed physical examination and imaging examination were preformed on this HME family,and clinical data and DNA samples were collected.PCR amplification and DNA sequencing were used to sequence the coding regions and intron-exon boundaries of EXT1 and EXT2 genes in this pedigree.Results: We find a novel frameshift muation c.660 del G(p.L221Cfs*82)in EXT2 gene by detecting the coding region of EXT1 and EXT2 in the proband.The novel mutation c.660 del G can lead to the truncated EXT2 protein with only 301 amid acid,resulting in the dysfunction of EXT2 protein.Subsequently,family members,who were also affected with HME,were detected and identified to exhibit this mutation in EXT2 gene.None of the unaffected family members exhibited this mutation.In this family,the co-separation of the mutation site and the disease indicated that the novel frameshift mutation c.660 del G in EXT2 gene was the cause of the occurrence of HME.Conclusion: The novel mutation c.660 del G in EXT2 gene is responsible for the occurrence of HME,also offers an effective theoretical basisfor genetic counseling and prenatal diagnosis in this family.