Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort

Figures

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  Figure 1. Detailed pedigree of the three families studied in this cohort. (A) Family A (FGD0128), (B) Family B (FGD0137) and (C) Family C (FGD0314). Individuals for whom whole exome sequencing was performed are highlighted with an asterisk (*). Square represents the males and the circles represent the females. Filled squares and the circles represent the affected individuals. Square or circles with question mark (?) represent the individuals with unknown phenotype. SCD represents the individual who had sudden cardiac death and “Pacemaker” represents the individuals who underwent pacemaker implantation.

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  Figure 2. Typical example of an ECG and Echocardiogram of one of the patients with PRKAG2 cardiomyopathy. ECG of patient BIII-4 shows a short PR interval with a delta wave (WPW pre-excitation pattern) and markedly high voltages indicating left ventricular hypertrophy in the QRS complexes with deep T wave inversions (A). Transthoracic echocardiogram (apical four-chamber view) of patient AIV-2 showing marked hypertrophy of the left ventricle (IVS 28 mm; lateral wall 20 mm) along with right ventricular free wall hypertrophy (blue asterisk). Pacemaker lead visualized as highlighted by yellow asterisk (B). IVS Interventricular Septum

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  Figure 3. Cardiac MRI (SSFP Cine sequences) of patient CIII-5 showing marked hypertrophy in the region of the interventricular septum and lateral wall of the left ventricle (yellow asterisks) along with right ventricular free wall hypertrophy (red asterisk) in the apical four-chamber view (A). The two-chamber long-axis view shows patchy areas of mid-wall left ventricular late gadolinium enhancement in the anterior and inferior walls (yellow asterisks) (B).

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  Figure 4. Endomyocardial biopsy with Periodic acid Schiff stain (PAS) showing abundant magenta positive granules (white arrow) in the cardiomyocyte cytoplasm indicating glycogen deposition. Enlarged cardiomyocytes were observed (A). Endomyocardial biopsy in Panel A treated with diastase (PAS-D) show marked clearing of the excessive glycogen deposition (B).

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  Figure 5. Identification of casual variants in the three families in the study cohort. Flowchart depicting the analysis of exome data from all the affected and unaffected members from the families. PRKAG2 c. 905G > A (Arg302Gln) mutation was identified as the casual variant (A). The Arg302Gln variant was confirmed using sanger sequencing (in red) and represents one of the highly conserved residues across species. A total of 26 variants have been reported in the PRKAG2 protein so far, shown in black (B).

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  Figure 6. Kinship analysis of the 3 families showed that the families are completely unrelated and have no founder effects. Genotype of each individual was compared with all the other individuals. Kinship was scored on a scale of 0–0.5, where kinship score 0.5 represents the identical individual and 0 represents the completely unrelated individual.