Danon Disease: Entire LAMP2 Gene Deletion with Unusual Clinical Presentation—Case Report and Review of the Literature

Figures

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  Figure 1. (a) LAMP2 protein and domains. Schematic representation of LAMP2 protein’s predicted three-dimensional structure from AlphaFold, a courtesy of https://www.genecards.org accessible data. Some amino residues are depicted for illustration, and all others (except than 315Asn) are involved in Danon Disease. (b) Schematic illustration of HGMD LAMP2 mutations according to variant subtypes (nonsense, missense, frameshift, splice, deletions) and their LAMP2 exon location and distribution. The variant IDs in the specific location above exons are the key for the detailed molecular change as it appears in the Supplementary Materials (S. excel file-1).

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  Figure 2. Family pedigree presenting the affected (filled) and the unaffected (no fill) family members, with three miscarriages.

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  Figure 3. (a) Echocardiography of Case 1, short-axis view of the left ventricle showing mild hypertrophy, increased echogenicity, and normal contraction. (b) Four-chambers view (4cv) showing left ventricular (LV) hypertrophy with lateral wall involvement > septum, normal contraction, increased echogenicity, left atrial dilatation. (c) 4cv zoom of the left ventricle.

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  Figure 4. CMA analysis of Case 1 (a) and Case 2 (b), lower and upper blots, respectively. CMA of Case 1 identified deletion of 110.5 Kb on Xq24. (GRCh37)(Xq24(119513013_119623579)x0 (a). The same deletion was seen in a heterozygous state in his daughter (Case2) (b).

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  Figure 5. Case 2’s ECG results at the age of 18 months old, showing a WPW pattern.

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  Figure 6. All called variants are assigned a quality value for filtering. Based on validation studies, the pipeline showed precision and detection > 99% for SNVs in areas with coverage greater than 20× and high mapping quality.