Key result
Novel homozygous DSP nonsense variant identified as the cause of Carvajal syndrome in four siblings.
Case Report (n=12)
No
A novel homozygous nonsense variant in the DSP gene (c.4297C>T; p.Gln1433*) was identified as the cause of Carvajal syndrome in a consanguineous family with severe biventricular arrhythmogenic cardiomyopathy.
Supports DSP screening in consanguineous Carvajal families; leaves open broader genotype-phenotype correlations.
Introduction: Arrhythmogenic cardiomyopathy (ACM) is a myocardial disorder characterized by fibrofatty replacement of the myocardium and is associated with heart failure and sudden cardiac death. It can involve either ventricle, including left-dominant forms defined partly by genetic findings. Methods: We investigated a consanguineous family with four affected daughters presenting with ACM, epidermolytic palmoplantar keratoderma, and woolly hair. The two eldest siblings died suddenly during childhood. The remaining two affected siblings underwent genetic analysis using autozygosity mapping and whole-exome sequencing, followed by segregation analysis. Results: Autozygosity mapping identified a shared identity-by-descent (IBD) interval at the DSP locus on chromosome 6. Exome sequencing revealed a novel homozygous nonsense variant (c.4297C>T; p.Gln1433*; rs1554108283) in exon 23 of DSP. This variant introduces a premature termination codon within the region specific to transcript variant 1, sparing transcript variant 2. Both parents were heterozygous carriers. Cardiac imaging in the affected siblings demonstrated biventricular involvement, including left ventricular systolic dysfunction and right ventricular dilatation. Skin biopsy in one patient confirmed epidermolytic palmoplantar keratoderma. Conclusions: We describe a novel homozygous nonsense variant in the transcript 1-specific region of DSP causing Carvajal syndrome, characterized by severe biventricular ACM, epidermolytic palmoplantar keratoderma, and woolly hair, in a consanguineous Arabian family with four affected sisters.
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Al-Mutairi et al. (2026) conducted a case report in Carvajal syndrome (Arrhythmogenic cardiomyopathy) (n=12). Homozygous nonsense variant (c.4297C>T; p.Gln1433*) in exon 23 of DSP vs. Unaffected family members (wild-type or heterozygous carriers) was evaluated on Identification of the genetic cause of Carvajal syndrome in the family. A novel homozygous nonsense variant (c.4297C>T; p.Gln1433*) in the transcript 1-specific region of the DSP gene was identified as the cause of Carvajal syndrome in four affected female siblings.
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