Identification of novel TTN gene variant in a patient exhibiting severe dilated cardiomyopathy co-occurring with acute fibrinoid organizing pneumonia

• Published in: American journal of clinical pathology
• Main Authors: Ma, Weijie, Wright, Dana L, Parra, Ourania, Shah, Nidhi D, Black, Candice C, Baker, Michael L, Khan, Wahab A
• Format: Journal Article
• Language: English
• Published: England 24.08.2024
• Subjects: acute fibrinoid organizing pneumonia; Titin (TTN); dilated (familial) cardiomyopathy; next-generation sequencing; molecular autopsy
• ISSN: 0002-9173; 1943-7722; 1943-7722
• DOI: 10.1093/ajcp/aqae100

Dilated cardiomyopathy (DCM) is often hereditary, with 20% to 40% of nonischemic cases showing familial linkage, yet genetic testing is underused. This report describes an unreported pathogenic nonsense variant in the Titin (TTN) gene (NM_001267550.2:c.92603G>A) in a 24-year-old man with severe DCM and acute fibrinoid organizing pneumonia, highlighting a unique cardiopulmonary pathology. We conducted detailed gross, histopathologic, immunophenotypic, and exome-based DNA sequencing analysis in the workup of this case. We also included the patient's clinical and radiologic findings in our study. With rapid clinical deterioration and complex comorbidities, including substance abuse and psychiatric conditions, which precluded transplantation, the patient's cardiac function progressively worsened. Autopsy findings included extreme cardiomegaly, biventricular hypertrophy, and acute and chronic pericarditis. Significant pulmonary pathology consistent with acute fibrinoid organizing pneumonia was also noted. Molecular testing confirmed a deleterious maternally inherited TTN variant that was absent in the sibling of the proband and the extant medical literature, highlighting its rarity and significance. This case contributes to the ongoing body of work on the impact of TTN variants on DCM. It suggests a potential link between genetic variants and complex cardiac injury patterns, emphasizing the need for further investigation into the interplay between cardiomyopathy and pulmonary pathology.