Dilated cardiomyopathy associated with connective tissue disease harboring germline NOTCHs rare variant: two case reports and literature review

Abstract Background Dilated cardiomyopathy (DCM) is a complex disease with multiple etiologies, including ischemic and non-ischemic causes. Non-ischemic DCM encompasses etiologies such as autoimmune disorders and gene mutations. However, the coexistence of DCM, a rare genetic variant, and connective tissue disease (CTD) is seldom reported. Little is known about the clinical profiles of DCM and CTD, nor the possible pathogenesis caused by certain gene rare variants. Case presentation In this case report, we collected and summarized the clinical data for two independent cases of patients diagnosed with DCM and CTD and their exome sequencing data. The two cases carried novel heterozygous rare variants in NOTCH genes, c.3451G > A: p.D1151N in the NOTCH2 gene and c.2068G > A: p.G690R in the NOTCH1 gene. These variants have never been reported in the medical literature and were predicted to be damaging or disease-causing variants. Conclusion Although the direct contribution of these NOTCH rare variants in disease progression is challenging to establish, we believe that our comprehensive clinical observations and literature review would contribute to the understanding of dysregulated Notch signaling in DCM combined with CTD.