case_images: PMC11830736_01
case_images: (A) Transthoracic echocardiography and 4-chamber view made in 2011; concentric LV hypertrophy (19 mm wall thickness) an LA enlargement. (B) Chest leads during an episode of atrial fibrillation at the age 60 years. Right bundle branch block, in addition marked right axis deviation (not shown) and absence of low voltage QRS complexes.
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case_images: PMC11830736_01_fcvm-12-1462523-g001.jpg
case_images: F1
case_images: AF (CHA2DS2VASc score: 1). After echocardiographic examination, a pathologic LV wall thickening up to 19 mm was detected supporting the suspected diagnosis of HCM (Figure 1A). Furthermore, an ECG investigation revealed an episode of acute AF at the day of procedure (Figure 1B).
case_images: Immunohistochemical staining of transthyretin (green) of patient's endomyocardial biopsy from right ventricle representing the affected area of wtATTR (A) Kongo-red staining of patient's endomyocardial biopsy to determine amyloid structure of protein aggregates (red). Microscopic evaluation of the affected area revealed minor interstitial fibrosis and degenerative alterations of the myocardial tissue surrounded by fibrillary structures (B) optical genome mapping (OGM) exhibited an approximately 28,877 kb heterozygous insertion as structural variant on chromosome 14q11.2, which may partially affect the MYH6 and/or the MYH7 gene (C).
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case_images: PMC11830736_01_fcvm-12-1462523-g002.jpg
case_images: F2
case_images: Using optical genome mapping (OGM), an approximately 29,877 kb heterozygous insertion on chromosome 14q11.2, which partially affects the MYH6 and/or the MYH7 gene, was identified as a larger, structural variant (Figure 2C). Microscopic evaluation of the biopsied tissue revealed minor interstitial fibrosis and degenerative alterations of the myocardial tissue accompanied by fibrillary structures with a positive Kongo-red staining (Figure 2B). Additionally, immunohistochemical staining of the affected area was positive for transthyretin (Figure 2A).
case_images: Sanger sequencing of MYH6 exon 33 and MYH7 exon 34 from patient's DNA (A,B). In (A), red rectangles represent four base pairs of MYH6 exon 33 which differ from those in MYH7 exon 34. Black rectangles with black arrows represent two base pairs, which seem mutated and represent wild type sequence of MYH7 exon 34 (A). In (B), black rectangles with black arrows represent four base pairs, which seem mutated for MYH7 exon 34 and differ from those in MYH6 exon 33. Red rectangles represent two base pairs, which are wild type for MYH7 exon 34 and differ from those in MYH6 exon 33 (B) The light yellowish sequence represent an area of a possible cross-over event of MYH6 exon 33 and MYH7 exon 34 based on Sanger sequencing results of both exons and the position of base pair mismatches with the reference in these exons indicated by red and black rectangles. In (C), a schematic illustration is shown of a possible cross-over event in a 75 bp long sequence area of MYH6 exon 33 and MYH7 exon 34 in maternal ancestors of the patient based on family history of heart failure and Sanger sequencing results of patient DNA (C).
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case_images: PMC11830736_01_fcvm-12-1462523-g003.jpg
case_images: F3
case_images: Remarkably, further investigation by Sanger sequencing of the affected chromosomal region revealed a most likely crossover event between exon 33 of MYH6 and exon 34 of MYH7 potentially resulting in a fusion hybrid gene of both myosin proteins (Figures 3A-C).