Longitudinal Analysis Casts Doubt on the Presence of Genetic Anticipation in Heritable Pulmonary Arterial Hypertension

• DOI: 10.1164/rccm.201205-0886oc
• Publication Date: 2012-08-24T04:30:34Z
• Authors: Emma K. Larkin; John H. Newman; Eric D. Austin; Anna R. Hemnes; Lisa Wheeler; Ivan M. Robbins; James D. West; John A. Phillips; Rizwan Hamid; James E. Loyd
• Keywords: Anticipation (artificial intelligence); BMPR2; Pedigree chart

Analysis of the age onset in heritable pulmonary arterial hypertension (HPAH) has led to hypothesis that genetic anticipation causes younger and death subsequent generations. With accrual pedigree data over multiple decades, we retested this using analyses eliminate truncation exists with shorter duration follow-up.To analyze pedigrees families mutations bone morphogenetic protein receptor type 2 (BMPR2), afflicted two or more generations HPAH, eliminating time bias by including for whom have at least 57 years data.We analyzed 355 individuals BMPR2 from 53 Vanderbilt Pulmonary Hypertension Registry. We compared diagnosis affected (n = 249) generation within multigenerational disease. performed linear mixed effects models limited time-truncation restricting date birth before 1955. This allowed follow-up (1955-2012) mutation carriers develop also conducted Kaplan-Meier analysis include currently unaffected 106).Differences were found a biased included all present, but finding was eliminated when 57-year observation limit imposed. By analysis, inclusion strengthens ascertainment recent are included.Genetic is likely an artifact incomplete kindreds HPAH due mutations.