BMPR2 Mutations in Six Taiwanese Patients with Idiopathic Pulmonary Arterial Hypertension

Background: Mutations in bone morphogenetic protein receptor type II (BMPR2) and activin-like kinase 1 (ALK1), have been implicated in the pathogenesis of heritable or idiopathic pulmonary arterial hypertension (HPAH/IPAH). However, there was still a lack of information regarding the underlying genetic factors in Taiwanese PAH patients. Methods: A total of 6 patients diagnosed with IPAH were enrolled in this study. The entire protein-coding region and intron/exon boundaries of the BMPR2 and ALK1 genes were amplified by polymerase chain reaction and analyzed by direct sequencing. Results: We identified 3 patients with BMPR2 heterozygous exonic mutations. One was a missense mutation, R491W. The second was a 2-base pair (bp) TG deletion at positions 1446 and 1447 relative to the translation start site. The third was a 2-bp CA deletion replaced by a single nucleotide T insertion at positions 991 and 992. The latter two mutations are novel and expected to result in frame shifts and premature termination. None of these 6 patients carried exonic mutations in the ALK1gene. Conclusion: A substantial portion of Taiwanese IPAH patients carry BMPR2 mutations. Since mutations in BMPR2 may be heritable and are associated with poor prognosis, genetic screening for BMPR2 mutations may be necessary for Taiwanese IPAH patients.