Prevalence and clinical characteristics of Danon disease among patients with left ventricular hypertrophy and concomitant electrocardiographic preexcitation

Figure 1. Surface ECGs (25 mm/s, 5 mm/mV) and parasternal long‐axis echocardiogram views of three patients with Danon disease. (a) Resting ECG demonstrates sinus bradycardia (50 bpm), normal PR interval (150 ms) but with positive delta waves in leads I, II, III, V1, and V6, high voltage of the left ventricle and inverted T waves in patient 1. Echocardiogram demonstrates concentric LVH with an IVS thickness of 19 mm and a LVPW thickness of 24 mm. (b) Resting ECG demonstrates sinus rhythm, a short PR interval (95 ms) with positive delta waves in leads I, II, III, aVF, V3‐–V6, as well as negative deltas in leads aVL and V1, high voltage of the left ventricle and inverted T waves in patient 2. Echocardiogram demonstrates concentric LVH with an IVS thickness of 33 mm and a LVPW thickness of 31 mm. (c) Resting ECG demonstrates sinus rhythm, a PR interval of 120 ms with positive delta waves in leads I, II, III, aVF, and V2–V6 as well as biphasic (±) delta waves in lead V1, high voltage of the left ventricle and inverted T waves in patient 3. Echocardiogram demonstrates concentric LVH with an IVS thickness of 29 mm and a LVPW thickness of 23 mm. IVS: interventricular septum; LVH: left ventricular…

Figure 2. Sanger sequencing validated three LAMP2 mutations. (a) DNA chromatogram shows a 1‐bp duplication (c. 973dupC) of exon 8 in patient 1, resulting in a frameshift mutation and a premature stop code after introducing 24 extra amino acids (p. L325PfsX24). (b) DNA chromatogram shows an A‐to‐G substitution in the splice‐acceptor site of intron 1 in patient 2(IVS 1‐2A > G). (c) DNA chromatogram shows a 7‐bp duplication (c. 29–35dupCGGGCTC) of exon 1 in patient 3, leading in a novel frameshift mutation and a premature stop codon after introducing 19 extra amino acids (p. V15RfsX19). WT: wild type. Nomenclature in reference to GenBank Accession NM_002294.2

Figure 3. Histopathological analysis of endomyocardial biopsy and skeletal muscle biopsy from patients with Danon patients. Upper panels: Hematoxylin and eosin staining reveals hypertrophied myocytes with profound intracellular vacuolation (left panel, original magnification × 200); Masson's trichrome staining reveals mild interstitial fibrosis with blue color (right panel, original magnification × 200). Middle and lower panels: Electron microscopy shows myofibrillar disruption and intracytoplasmic vacuoles containing autophagicmaterial and glycogen

Figure 4. Immunofluorescent analysis of endomyocardial biopsy and skeletal muscle biopsy from patients with Danon patients. Immunofluorescence staining with LAMP2 antibody demonstrates complete absence of LAMP2 protein (red) in the skeletal muscle samples of patient 1 and severe decrease in both skeletal and cardiac muscle samples of patient 3