Key result
Sequencing reveals the first living adult Timothy syndrome patient with both CACNA1C and PKP2 variants.
Case Report (n=1)
This case expands the clinical and molecular spectrum of Timothy syndrome by identifying a novel CACNA1C mutation alongside a PKP2 mutation in an adult.
Novel CACNA1C variant in adult survivor with PKP2 variant; extends molecular spectrum but leaves open additive arrhythmia risk.
CANAC1C encodes for the main cardiac L-type calcium channel and mutations on it lead to a prolonged QT interval in Timothy Syndrome (TS). We provide a new de novo constitutional heterozygote missense variation in CACNA1C in a living adult woman, also carrier of the known c.2146-1G>C heterozygous variation of PKP2 inherited from her father. To our knowledge, this patient is the first to have the two variations in these genes. Theses clinical and molecular findings expand the clinical and molecular spectrum of TS and show the interest of next generation sequencing or whole exome sequencing in rare disorders, atypical or novel phenotype.
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Colson et al. (2019) conducted a case report in Timothy Syndrome (n=1). CACNA1C and PKP2 mutations was evaluated. A living adult woman with Timothy syndrome was identified as the first known carrier of both a new de novo missense variation in CACNA1C and a known heterozygous variation in PKP2.
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