Pedigree Investigation And Genetic Analysis Of Familial Atrial Septal Defect

Objective To study the clinic features and causative gene of three families with atrial septal defect.Methods Family members in three family of FASD were evaluated by history, review of medical records, physical examination, 12-lead electrocardiogram and transthoracic echocardiography. Techniques of polymerase chain reaction and direct sequencing were used to screen the mutation in candidate gene NKX2-5 in all members of three families.Results In family I, 16 individuals were affected by cardiovascular abnormalities, 12/16 had ASD and 12/16 had AVB. A heterozygous point mutation +1433 C→T was identified in the intron of NKX2-5 gene of affected individuals,but not in the unaffected members of the family and 24 sporadic cases and 300 normal people. In each of family II and family III, 3 individuals presented ASD, None causative mutation of NKX2-5 was found in the two family.Conclusion The most common phenotypes of family I were ASD and AVB, which suggest the family is affected by autosomal dominant FASDAVB. The novel missense mutation int+1433 C→T in NKX2-5 gene was responsible for family I. Family II and family III may be affected by SFASD.