Rare missense variants in the spectrin repeat domain of DSP were significantly enriched in cardiomyopathy cases compared to the gnomAD population (46% vs 30%; p=0.004).
Systematic Review (n=1,573)
Are rare missense variants in the spectrin repeat domain of DSP associated with arrhythmogenic cardiomyopathy?
Rare missense variants in the spectrin repeat domain of DSP are enriched in patients with arrhythmogenic cardiomyopathy, identifying a potential mutation hotspot that can aid in diagnostic variant interpretation.
Tasa de eventos absoluta: 46% vs 30%
valor p: p=.004
Rare loss of function variants in DSP, which codes for the desmosomal protein desmoplakin, have been implicated in dilated and arrhythmogenic right ventricular cardiomyopathies. We present a family with arrhythmogenic cardiomyopathy associated with a novel missense variant in DSP (NM₀04415. 4): c. 877G>A, p. (Glu293Lys). The phenotype is characterized by predominant involvement of the left ventricle with systolic dysfunction, fibrosis, and life-threatening arrhythmias. We performed a systematic review of literature collecting all cardiomyopathy cases with rare missense variants in DSP. We demonstrate that the distribution of missense variants across the protein domains in cardiomyopathy cases differs from that in gnomAD (p =. 04), with a case enrichment of rare missense variants in the spectrin repeat domain (36/78 46% in cases vs. 449/1495 30% in gnomAD; p =. 004). Our findings highlight the predominance of cardiac arrhythmia and left ventricular involvement in desmoplakin cardiomyopathy and pinpoint to a potential mutation hotspot in DSP thereby facilitating missense variant interpretation in the diagnostic setting.
Grondin et al. (Tue,) conducted a systematic review in Arrhythmogenic cardiomyopathy (n=1,573). Rare missense variants in the spectrin repeat domain of DSP vs. gnomAD population was evaluated on Presence of rare missense variants in the spectrin repeat domain (p=.004). Rare missense variants in the spectrin repeat domain of DSP were significantly enriched in cardiomyopathy cases compared to the gnomAD population (46% vs 30%; p=0.004).