Case report: Whole-exome sequencing identifies a novel DES mutation (p. E434K) in a Chinese family with cardiomyopathy and sudden cardiac death

Figures

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  FIGURE 1. The clinical and sequencing data of this family. (A) The genealogy of this family. Squares indicate male family members and circles indicate female members. The black symbols represent the clinically affected members. The white symbols represent unaffected and healthy members. The arrow shows the proband. Crossed-out symbols stand for deceased relatives. ± represents heterozygous DES-p. E434K variant. + / + represents a wild type. (B) ECG of the proband. (C) Sanger DNA sequencing chromatogram detected a heterozygous mutation (c.1300G > A; p. E434K) of DES gene in the proband. (D) Alignment of multiple DES protein sequences across species. Letters in red show the E434 site is evolutionarily conserved.

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  FIGURE 2. The bioinformatics analysis of mutations. Structure prediction of the mutant protein. The wild-type DES (DES-WT) protein structure and the p. E434K mutant DES (DES-p. E434K) protein structure were predicted by SWISS-MODEL online software. (A) Red arrow shows the charged change of desmin protein. In the DES-WT protein, E434 is hydrophobic with S432 and R436. In the DES-p.E434K protein, the hydrophobic effect with S432 disappeared after E434K mutation, while the hydrophobic effect with R436 remained (B) MetaDome server was used to identify the intolerant regions in DES. As depicted, the affected nucleotide/residue is located in an intolerant region. (C) Overview of all reported phenotypes caused by DES mutations. ARVC, arrhythmogenic right ventricular cardiomyopathy; AVP, autophagic vacuolar pathology; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LVNC, left ventricular non-compaction; RCM, restrictive cardiomyopathy; SCD, sudden cardiac death; SUD, sudden unexplained death.