An interesting Mybpc3 heterozygous mutation associated with bicuspid aortic valve

Figures

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  Figure 1. Twelve-lead electrocardiogram (ECG) and ultrasonic cardiogram in the bicuspid aortic valve (BAV) patient. (A) 12-lead ECG in resting time showed sinus arrhythmia, and left ventricular was a little hypertrophy (RV5 =42 mm); (B,C) ultrasonic cardiogram in the BAV patient.

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  Figure 2. Family pedigree and the filtering process for WES data. (A) The family pedigree consists of two probands. I-1 represents the proband’s mother, I-2 represents the proband’s father; II-1 represents the proband; (B) The filtering process for WES data. It contains 94,394 total coding variants. Then filtered 2,840 common variants, 801 deleterious variations, 18 genetic analysis, final 1 associated with this phenotype variation.

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  Figure 3. The Mybpc3 mutation site and its expression. (A) Human Mybpc3 gene maps to chromosome 11p11.2 and contains 34 exomes. The base pair mutation site is c.173C>T, which is located in the second exome of Mybcp3. (B) The proband and her father were confirmed to be heterozygous carriers of 173 C>T hybridization, and her mother was homozygous negative of the mutation as showed through Sanger sequencing. (C) Relative Mybpc3 mRNA levels before and after the mutation. (D) C. 173C>T mutation is in a highly conservative area of cross-species. (E) Mybpc3 protein levels in the proband and her father were almost half of proband’s mother.

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  Figure 4. Prediction of the mutation on its functional. (A) Wild type of Mybpc3 protein structure. (B) Mutant of Mybpc3 protein structure. (C) STRUM server indicated that the Ala58Val mutation may affect Mybpc3 protein stability. (D) Alternative interpretation is that the effect of the Mybpc3 N-terminal fragment is caused by an interaction with thin filament. The coiled-coil part of myosin is shown in light blue; S1 and S2, in pink; Mybpc3, in red; and F-actin, in light green.