Increased Ca_V1.2 late current by a CACNA1C p.R412M variant causes an atypical Timothy syndrome without syndactyly.

ABSTRACT: 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 (Ca_v1.2), 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 Ca_V1.2 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

SUBMITTER: Ozawa J 

PROVIDER: S-EPMC9643354 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature