ABSTRACT
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.
Subject(s)
Autistic Disorder/genetics , Calcium Channels, L-Type/genetics , Long QT Syndrome/genetics , Phenotype , Syndactyly/genetics , Adult , Autistic Disorder/pathology , Female , Heterozygote , Humans , Long QT Syndrome/pathology , Mutation , Plakophilins/genetics , Syndactyly/pathologyABSTRACT
QT and Tp/Te intervals were longer in patients with LQT1 (n = 67) than in nonaffected subjects (n = 52) but did not differentiate symptomatic (n = 21) from asymptomatic patients (n = 46). At fast heart rate, the time to accumulate the last part of total T-wave area (the t50-97 interval) was longer in symptomatic carriers compared with asymptomatic patients (119 +/- 19 vs 106 +/- 15 ms, p <0.01). The latter group had significantly longer t50-97 intervals than nonaffected subjects (96 +/- 14 ms, p <0.01).
