Key result
A novel homozygous frameshift mutation at the extreme C-terminal region of the DSP gene caused severe arrhythmogenic left ventricular cardiomyopathy without dermatological symptoms.
Case Report (n=4)
A novel truncating variant at the extreme C-terminal region of desmoplakin causes severe arrhythmogenic left ventricular cardiomyopathy without cutaneous manifestations, highlighting the functional importance of this protein domain.
Expands DSP cardiomyopathy spectrum to isolated severe ALVC; leaves open whether extreme C-terminal truncations define distinct phenotypes.
BACKGROUND: Homozygous truncating mutations located in the C-terminal region of the desmoplakin gene (DSP) are known to mainly cause Carvajal syndrome, an autosomal recessive syndromic form of arrhythmogenic cardiomyopathy with an extra-cardiac cutaneous phenotype. CASE PRESENTATION: Here we describe a female proband with a documented arrhythmogenic left ventricular cardiomyopathy and a syncopal episode at the age of 13, who was found homozygous for the novel DSP variant: NM_004415.4:c.8586delC, p.(Ser2863Hisfs*20) at the extreme C-terminal region of the protein, just 8 amino acids upstream the stop codon. She did not have any of the typical dermatological symptoms that characterize Carvajal syndrome. Her brother had died suddenly at the age of 18 during exercise and was found homozygous for the same variant at the post-mortem, while their parents were heterozygous. The region of origin of both parents was the same geographic area of Greece, but they were not aware of any common ancestor. Detailed clinical examination revealed that the mother displayed a mild arrhythmic phenotype, while the father was asymptomatic. CONCLUSION: These observations pinpoint to a significant functional role of the extreme C-terminal tail of the protein.
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Pantou et al. (2023) conducted a case report in Arrhythmogenic cardiomyopathy (n=4). Homozygous truncating mutation in DSP (NM_004415.4:c.8586delC) vs. Heterozygous carriers (parents) was evaluated on Clinical phenotype. A novel homozygous frameshift mutation at the extreme C-terminal region of the DSP gene caused severe arrhythmogenic left ventricular cardiomyopathy without dermatological symptoms.
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