Determination Of Mutations In ALK-1 Gene And ENG Gene In A Chinese Family With Hereditary Hemorrhagic Telangiectasia Disease

Objective To identify the gene mutations and investigate the clinical features of a pedigree with hereditary hemorrhagic telangiectasia.Methods(1)Proband of the first diagnosed HHT and her families were be investigated;(2) All the ALK-1 and ENG gene's exons of the proband,were amplified by polymerase chain reaction(PCR);(3) The PCR products were screened by direct sequencing.;(4) According to the determinate mutations from the results of sequence analysis,the PCR product of corresponding exon were be conducted site-specific restriction enzyme test.Results(1)In the investigated 62 members of the family including a total of 5 on behalf,19 members had spontaneous recurrent epistaxis;No spontaneous bleedimg history existed in other 43 members.45 family members of the pedigree carried out molecular biology test,which 14 family members have varying degrees repeated epistaxis.(2) 19 family members with repeated epistaxis began to epistaxis at the age of 6 to 15 years old,began to appear epistaxis at the average age about 11 years old,which included 12 men and 7 women;the 19 family members with repeated epistaxis have none other sites bleeding.(3)The PCR detection which is regarding 45 family members and 30 healthy volunteers,obtained a single and correct size band about all exons of ALK-1 gene and ENG gene.(4) The 14 members repeated epistaxis who participated the test exist G207A mutation of ENG gene by sequence analysis, but The G207A mutation does not exist in the other 31 family members and 30 healthy volunteers(5) The restriction endonuclease results showed that the PCR product of the 14 patients who existence G207A mutation mutation can not be cut off completely by restriction endonuclease GsuI;however,the PCR product of the other 31 no epistaxis family members and 30 healthy volunteers were can be cut off completely by restriction endonuclease GsuI.Conclusion(1) This pedigrees which is in line with the autosomal dominant genetic disease characteristics,can be identified as the HHT pedigrees.(2)The HHT patients of the HHT pedigrees exist G207A mutation in of ENG gene.(3) In the HHT pedigrees,the G207A mutation of the HHT patients may be the cause of HHT or the result of HHT;The exact relationship between G207A mutation and HHT should be further research.