Case Report: Novel LIM domain-binding protein 3 (LDB3) mutations associated with hypertrophic cardiomyopathy family

Figures

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  Figure 1. Echocardiography in HCM probands. (A) Echocardiography of a proband: slight left ventricular hypertrophy at later observation (red arrow). (B) Echocardiography of a proband: enlargement of left atrial (blue arrow) and left ventricle (red arrow) at first time. (C,D) Echocardiography of a proband: slight left ventricular hypertrophy (red arrow).

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  Figure 2. Family pedigrees and filtering processes for WES data. (A) One pedigree consists of one proband and three members. I-1 represents the proband's mother. I-2 represents the proband's father. II-1 represents the proband. II-2 represents the proband's sister. (B) The filtering process for WES data. It contains 80,192 total coding variants. Then, 1,695 common variants, 793 deleterious variations, 32 genetic analyses, and final 4 associated with this phenotype variation were filtered. TGFB3:NM_001329938:exon2:c.C487T: p.R163W, LMNA:NM_005572:exon10:c.G1712A: p.R571H, MYH7:NM_000257: exon3:c.C77T: p.A26V were deleted. (C) One pedigree consists of one proband. I-1 represents the proband's mother. I-2 represents the proband's father. II-1 represents the proband. (D) The filtering process for WES data. It contains 77,925 total coding variants. Then, 1, 745 common variants, 797 deleterious variations, 30 genetic analyses, final 1 associated with this phenotype variation were filtered.

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  Figure 3. The LDB3 mutation site and Sanger sequencing. (A) Human LDB3 gene maps to chromosome 10q23.2 and contains 16 exomes. The base pair mutation site is c.967C > T (p.P323S), which is located in the 10th exome of Mybcp3. The base pair mutation site is c.1655G > A, which is located in the 12th exome of Mybcp3. (B) The proband and her father were confirmed to be heterozygous carriers of 1655 G > A hybridization. Her mother and sister were homozygous negative of the mutation. (C) The other proband was confirmed to be heterozygous carriers of 967 C > T hybridization. His parents were homozygous negative of the mutation as showed through Sanger sequencing.

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  Figure 4. Prediction of the mutation on its functional. (A,B) The location of the mutation (c.967C > T, c.1655G > A) in the LDB3 gene. (C) c.967C > T mutation region locates in a highly conserved area of cross-species. (D,E) STRUM server indicated that the P323S and R547Q mutation may affect LDB3 protein stability.