Tremendous progress has been made in understanding the genetics of pulmonary arterial
hypertension (PAH) since its description in the 1950s as a primary disorder of the
pulmonary vasculature. Heterozygous germline mutations in the gene coding bone morphogenetic
receptor type 2 (BMPR2) are detectable in the majority of cases of heritable PAH,
and in approximately 20% of cases of idiopathic pulmonary arterial hypertension (IPAH).
However, recent advances in gene discovery methods have facilitated the discovery
of additional genes with mutations among those with and without familial PAH. Heritable
PAH is an autosomal dominant disease characterized by reduced penetrance, variable
expressivity, and female predominance. Biallelic germline mutations in the gene EIF2AK4
are now associated with pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.
Growing genetic knowledge enhances our capacity to pursue and provide genetic counseling,
although the issue remains complex given that the majority of carriers of PAH-related
mutations will never be diagnosed with the disease.
Keywords
bone morphogenetic protein receptor type 2 - caveolin-1 -
KCNK3
-
CBLN2
-
TBX4
-
EIF2AK4
- pulmonary arterial hypertension - genetic modifiers - hereditary hemorrhagic telangiectasia
