case_images: PMC11157066_01
case_images: Clinical imagines of the proband. (A) Echocardiography demonstrated extremely enlarged bilateral atrium (left atrium dimeter 3.94 x 6.84 cm, right atrium dimeter 4.86 x 6.14 cm), interventricular septum segmentally thickened, partial ventricular wall pulse amplitude segmentally diffusely reduced and uncoordinated, mild mitral regurgitation, reduced left ventricular systolic and diastolic function. (B) Electrocardiogram revealed abnormal bilateral atrial signals, premature atrial beat, junctional ectopic beat, first degree atrioventricular block, complete right bundle branch block, prolonged QT interval, and abnormal Q wave. (C) Electrocardiogram presented persistent AF had been identified after ECMO withdraw.
case_images: fcvm-11-1365209-g001.jpg
case_images: PMC11157066_01_fcvm-11-1365209-g001.jpg
case_images: F1
case_images: Echocardiography revealed an extremely enlarged bilateral atrium (left atrium diameter 3.94 x 6.84 cm, right atrium diameter 4.86 x 6.14 cm), segmental thickening of the interventricular septum, segmentally diffuse reduction and lack of coordination in ventricular wall pulse amplitude, mild mitral regurgitation, and diminished left ventricular systolic and diastolic function identified by increased parameters of early diastolic velocity (E wave) and low late filling velocity (A wave) (Figure 1A). Electrocardiogram findings displayed abnormal bilateral atrial signals, premature atrial beats, junctional ectopic beats, first-degree atrioventricular block, complete right bundle branch block, prolonged QT interval, and abnormal Q wave (Figure 1B). Subsequent to ECMO withdrawal during hospitalization, persistent atrial fibrillation (AF) was observed (Figure 1C).
case_images: The TNNI3 molecular analysis. (A) The proband exhibited a de novo heterozygous variant of TNNI3 (c.509G>A, p.R170Q). (B) The variant of TNNI3 c.509G>A had never reported in 1000G and ExAC, it has predicted protein damaging by PolyPhen-2 and SFIT. (C) The protein structure of cTnI has been built and named AF-P19429-F1. (D) Localized structural views had been established by SWISS-MODEL for cTnI-R170Q, R170W and R170G based on Q8MKD5.1.A template, respectively. (E) Comparisons had been made on the structural impaired among cTnI-R170Q, R170W and R170G. Based on the ensemble variance analysis, we found that the cTnI-R170Q and R170W shared the similar impacts on protein structural stability and formation. However, both of them presented significant differences with cTnI-R170G, mainly influencing the regions of 32-79 and 129-149 amino acids, which were involved in TnC and actin binding.
case_images: fcvm-11-1365209-g002.jpg
case_images: PMC11157066_01_fcvm-11-1365209-g002.jpg
case_images: F2
case_images: According to the analysis result of WES, a de novo heterozygous variant had been identified as c.509G>A (p.R170Q) of TNNI3 gene (Figure 2A). And the variant of TNNI3 c.509G>A was never reported in database which was considered as a novel variant (Figure 2B). TNNI3) which had been analyzed by x-ray or cryo-EM, AlphaFold protein structure software (https://alphafold.ebi.ac.uk/) tool had been used to predicted protein crystal structure. The protein structure of cTnI has been built and named AF-P19429-F1 (Figure 2C). Localized structural views had been established by SWISS-MODEL for cTnI-R170Q, R170W and R170G based on Q8MKD5.1.A template, respectively (Figure 2D). Then we compared the structural impaired among cTnI-R170Q, R170W and R170G (Figure 2E).