Journal List > Lab Med Online > v.8(3) > 1097046

Kim, Lee, Jekarl, Chae, Kim, Jung, and Jeon: Clinical Presentation with High Penetrance in a Korean Family with Pulmonary Arterial Hypertension Associated with a BMPR2 Intron 3 Splice Site Pathogenic Variant

Abstract

Pathogenic variants of bone morphogenic protein receptor type 2 gene (BMPR2) are related to the majority of cases of heritable pulmonary arterial hypertension (PAH). Over 400 pathogenic variants have been identified. However, clinical characterization of PAH is still incomplete. We present a case of heritable PAH in a Korean family showing serious clinical presentation with high penetrance. Genetic sequencing revealed a known heterozygous BMPR2 pathogenic variant, c.418+5G>A, at a splice site of intron 3. Serious clinical presentation with high penetrance suggested that the interplay of other factors with pathologic variants might be in genotype-phenotype correlation. Further studies are needed to clarify these issues for the development of personalized medicine approaches for PAH.

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Fig. 1.
Pedigree of the case family. The proband (II:3) was diagnosed with PAH later than her fourth (III:4) and fifth (III:5) daughters. Numbers in parentheses are age at death or current living age.
lmo-8-119f1.tif
Fig. 2.
Chest radiograph, electrocardiogram, and echocardiogram of the proband at the time of PAH diagnosis. Cardiomegaly with bilateral hilar enlargement in chest radiograph (A), atrial fibrillation and right ventricular hypertrophy in electrocardiogram (B), right ventricular dilation and hypertrophy, interventricular septal bowing (arrowhead), resultant left ventricular compression, and small amount of pericardial effusion in echocardiography (C-E). Estimated systolic pulmonary arterial pressure from peak tricuspid regurgitation flow velocity is around 110 mmHg (F). Abbreviations: AO, aorta; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
lmo-8-119f2.tif
Fig. 3.
Chest radiograph and echocardiogram of the proband's fourth daughter (III:4) and first daughter (III:1) at the time of PAH diagnosis. Cardiomegaly and hilar enlargement in X-ray (A, E), right ventricular dilation and hypertrophy, interventricular septal bowing to left ventricle (arrow head) in echocardiogram (B-D, F-H). Abbreviations: AO, aorta; LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.
lmo-8-119f3.tif
Fig. 4.
Sequencing chromatogram of BMPR2 gene from proband (A), proband's first daughter (III:1, B), and unaffected third daughter 5 (III:3, C) showed identical heterozygous pathogenic variants c.418+5G>A in the splice site of intron 3.
lmo-8-119f4.tif
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