Identification of a novel mutation in the BMPR2 gene in a pulmonary arterial hypertension patient using next‐generation sequencing

Figures

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  FIGURE 1. Genome sequencing revealed a heterozygous c.1481C>T mutation in the BMPR2 gene, which causes amino acid p. Ala494Val. No additional mutation was found

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  FIGURE 2. Phylogenetic conservation analysis. Evolution conservation analysis revealed that p.A494 in the BMPR2 domain was extremely evolutionarily conserved

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  FIGURE 3. Predicted secondary structure and solvent accessibility predicted by I‐TASSER server. Secondary structures of normal and mutant amino acid are predicted to be helix at position 494 with the respective confidence score of 8 and 9, the confidence ranges 0–9 wherein a higher score indicates a prediction with higher confidence. The solvent accessibility of the sequence is predicted as buried amino acid (range 0–9 wherein a higher value means higher accessibility)

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  FIGURE 4. Bioinformatics analysis. The results of protein function prediction, Pfam, reveals the domain contained in the protein sequence (A). Secondary structure simulation showed the relative position of α, β, and random curl (B)

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  FIGURE 5. Protein‐protein interaction network of bone morphogenetic protein type II receptor (BMPR2). Predicted functional partners are as follows: BMP7: bone morphogenetic protein 7 (431 aa); BMP2: bone morphogenetic protein 2, induces cartilage and bone formation (396 aa); ACVR1: activin receptor type‐1 (509 aa); GDF2: growth/differentiation factor 2 (429 aa); BMP4: bone morphogenetic protein 4, induces cartilage and bone formation (408 aa); BMP6: bone morphogenetic protein 6, induces cartilage and bone formation (513 aa); SMAD4: mothers against decapentaplegic homolog 4 (552 aa); SMAD6: mothers against decapentaplegic homolog 6 (496 aa); SMAD9: mothers against decapentaplegic homolog 9 (467 aa); and SMAD5: mothers against decapentaplegic homolog 5 (465 aa)