摘要Background Familial pulmonary arterial hypertension(FPAH)js an autosomal dominant disorder characterized by plexiform lesions of endothelial cells in pulmonary arterioles which leads to elevated pulmonary arterial pressure,right-sided heart failure and death.Heterozygous mutations in the bone morphogenetic protein type Ⅱ receptor gene (BMPR2)have been found to underlie a majoritv of FPAH cases.More than 140 distinct mutations have been identified in FPAH cases and in idiopathic pulmonary arteriaf hypertension(IPAH)cases,but only one mutation has been reported in Chinese patients.Methods A three-generation pedigree of FPAH and another 10 patients with IPAH were collected.In the family.two of the 9 surviving and one deceased family member were diagnosed as FPAH.The entire protein-coding region and intron/exon boundaries of the BMPR2 gene were amplified by PCR using DNA samples from affected individuals.Direct sequencing of PCR products was performed on both the sense and antisense strands.To confirm the segregation of the mutation within the family and exclude the presence of the mutation in normal subjects,the relevant exon was amplified by PCR,followed by mutation-specific RPLP analysjs.Results In the Chinese pedigree with FPAH an A-to-T transition at position 1157 in exon 9 of the BMPR2 gene was identified which resulted in a Glu386Val mucation.We confirmed the segregation of the mutation within the family and excluded the presence of the mutation in a panel of 200 chromosomes from normal subjects.No mutation was detected in BMPR2 in the other 10 patients with IPAH.Conclusions This amino acid substitution occurs at a glutamic acid that is highly conserved in all type Ⅱ TGF-βreceptors.The nearly invariant Glu forms an ion pair with an invariant Arg at position 491 thereby helping to stabilize the large Iobe.Substitution of Arg at position 491 is the most frequently observed missense mutation in FPAH,but until now no mutations at position 386 have been found in FPAH.The predicted functional impact of the Glu386Val mutation and its absence in healthy controls support the mutation as the cause of FPAH.