Heritable pulmonary arterial hypertension (HPAH) – high pressure in the blood vessels leading from the heart to the lungs – is a rare, lethal disease. Most families with HPAH have mutations in the BMPR2 gene. Studies have suggested that “genetic anticipation” – progressively earlier onset and increased severity of disease in successive generations of affected families – is a feature of HPAH.
Now, Emma Larkin, Ph.D., James Loyd, M.D., John Newman, M.D., and colleagues report a new analysis that casts doubt on genetic anticipation in HPAH. They analyzed 355 individuals with BMPR2 mutations from 53 families in the Vanderbilt Pulmonary Hypertension Registry. Limiting their analysis to family members born before 1955 allowed for 57 years of observation for disease diagnosis.
They report in the Nov. 1 American Journal of Respiratory and Critical Care Medicine that genetic anticipation may not exist in BMPR2-related HPAH and was likely detected in earlier studies as an artifact of incomplete time of observation. The findings inform families that the risk of earlier disease is not passed on to the next generations.
This research was supported by grants from the National Heart, Lung, and Blood Institute (HL093363, HL098743, HL102020, HL095797) and from the National Center for Research Resources/National Center for Advancing Translational Sciences (RR024975) of the National Institutes of Health.
