@article{oai:shiga-med.repo.nii.ac.jp:00004379,
 author = {小澤, 淳一 and 大野, 聖子 and 福山, 恵 and 豊田, 太 and 堀江, 稔 and OZAWA, Junichi and OHNO, Seiko and MELGARI, Dario and WANG, Qi and FUKUYAMA, Megumi and TOYODA, Futoshi and MAKIYAMA, Takeru and YOSHINAGA, Masao and SUZUKI, Hiroshi and SAITOH, Akihiko and HORIE, Minoru},
 issue = {1},
 journal = {Scientific Reports},
 month = {Nov},
 note = {application/pdf, application/docx, Timothy syndrome (TS) is a rare pleiotropic disorder associated with long QT syndrome, syndactyly, dysmorphic features, and neurological symptoms. Several variants in exon 8 or 8a of CACNA1C, a gene encoding the α-subunit of voltage-gated Ca2+ channels (Cav1.2), are known to cause classical TS. We identified a p.R412M (exon 9) variant in an atypical TS case. The aim of this study was to examine the functional effects of CACNA1C p.R412M on CaV1.2 in comparison with those of p.G406R. The index patient was a 2-month-old female infant who suffered from a cardio-pulmonary arrest in association with prolonged QT intervals. She showed dysmorphic facial features and developmental delay, but not syndactyly. Interestingly, she also presented recurrent seizures from 4 months. Genetic tests identified a novel heterozygous CACNA1C variant, p.R412M. Using heterologous expression system with HEK-293 cells, analyses with whole-cell patch-clamp technique revealed that p.R412M caused late Ca2+ currents by significantly delaying CaV1.2 channel inactivation, consistent with the underlying mechanisms of classical TS. A novel CACNA1C variant, p.R412M, was found to be associated with atypical TS through the same mechanism as p.G406R, the variant responsible for classical TS., Journal Article},
 title = {Increased CaV1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly},
 volume = {12},
 year = {2022}
}