Penetrance of pulmonary arterial hypertension is modulated by the expression of normal BMPR2 allele.

Hamid R, Cogan JD, Hedges LK, Austin E, Phillips JA, Newman JH, Loyd JE
Hum Mutat. 2009 30 (4): 649-54

PMID: 19206171 · PMCID: PMC2663001 · DOI:10.1002/humu.20922

Familial pulmonary arterial hypertension (FPAH) is a progressive, fatal disease caused by mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2). FPAH is inherited as an autosomal dominant trait, and shows incomplete penetrance in that many with BMPR2 mutations do not develop FPAH, suggesting a role for, as yet unidentified, modifier genes in disease penetrance. We hypothesized that variable levels of expression of the wild-type (WT) BMPR2 allele could act as a modifier and influence penetrance of FPAH. WT BMPR2 levels were determined by real-time PCR analysis in lymphoblastoid (LB) cell lines derived from normal controls and individuals with FPAH. The FPAH kindreds analyzed carried mutations that result in the activation of nonsense-mediated decay (NMD) pathway, which leads to the degradation of the mutant RNA, thus ensuring that only the WT BMPR2 transcripts will be detected in the real-time assay. Our data show that WT and mutant BMPR2 levels can be reproducibly measured in patient-derived LB cell lines, and that unaffected mutation carrier-derived LB cell lines have higher levels of WT BMPR2 transcripts than FPAH patient-derived LB cell lines (p
(c) 2009 Wiley-Liss, Inc.

MeSH Terms (12)

Alleles Blotting, Western Bone Morphogenetic Protein Receptors, Type II Cell Line, Transformed Family Health Gene Expression Genotype Humans Hypertension, Pulmonary Mutation Penetrance Reverse Transcriptase Polymerase Chain Reaction

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