PMC10285293_01
Fetal sonography and pathological findings of the proband's heart. (A) Fetal echocardiography at 26 + 0 weeks of gestation during the second pregnancy. (B) Fetal echocardiography at 25 + 4 weeks of gestation during the third pregnancy. The asterisk indicates the severely thickened myocardium, and the white arrows show the blood flow into the deep intertrabecular recesses of the left ventricle. (C) Fetal sonography showing marked subcutaneous edema and right pleural effusion in the proband. (D) Hematoxylin and eosin staining of the horizontal section of the middle level of the ventricular long axis of the autopsy. Remarkable trabeculation of the left ventricle is detected. (E) The solid bidirectional arrow shows the compacted layer, and the dotted bidirectional arrow shows the thickened non-compacted layer of the left ventricle. (F) Histological appearance with Azan staining reveals fibrosis of the endocardium of the left ventricle. The endocardium is stained blue more intensely. RA, right atrium; RV, right ventricle; LA, left atrium; LV, left ventricle.
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F1
Fetal echocardiography at 26 + 0 weeks of gestation is shown in Figure 1A. Fetal echocardiography is shown in Figure 1B. The hydropic signs worsened during the course of the pregnancy (Figure 1C). Histological examination of the left ventricle revealed a two-layered structure composed of a prominent trabeculated and compacted layer (Figures 1D, E), and endocardial elastic fibrous proliferation throughout the left ventricle (Figure 1F).
DNA sequencing analysis of proband's whole blood (A) and the pedigree of this family (B). The black arrow indicates the proband (II-4).
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F2
T, p.Lys910Ile, which had not been reported in several genetic databases, including ClinVar, HGMD , dbSNP, gnomAD, and Jmorp (Japanese Multi Omics Reference Panel) (Figure 2A). The GADD score and PolyPhen-2, which predicted the effect of a variant on protein function, showed that this novel MYH7 variant was pathogenic. The pedigree is shown in Figure 2B.
Direct sequencing trio analysis chromatograms. A red circle indicates a slight change (c.2729A > T) of unclear significance.
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F3
T) of unclear significance was detected in the chromatogram (Figure 3).
Diagram of the workflow from the delivery of the previous fetus (II-3) to parental sequencing.
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F4
Figure 4 illustrates the workflow from the delivery of the previous fetus (II-3) to parental sequencing.