TABLE 1.
Presentation of the 18 CACNA1G variants investigated in the study in automated patch-clamp (APC), manual patch-clamp (MPC) or both (APC/MPC). The clinical description of the variants in black can be found in previous studies (see references).
| Variants | MPC/APC tested | Inheritance | Clinical information |
|---|---|---|---|
| p.R102Q | APC | not known | Ataxia, progressive cerebellar atrophy, global developmental delay. Medical history complicated by prenatal exposures to drugs/alcohol. Possible encephalitis in infancy. Variant also present in EXAC. |
| p.V184G | APC | not known | Adult-onset neuromuscular disease, including ptosis, muscle weakness, peripheral neuropathy, and ataxia |
| p.M197R | APC/ MPC | de novo | Qebibo et al. (2024) |
| p.L208P | APC | de novo | Berecki et al. (2020) |
| p.V392M | APC/MPC | de novo | Qebibo et al. (2024) |
| p.F956del | APC/ MPC | de novo | Qebibo et al. (2024) |
| p.A961T | APC/MPC | de novo | Chemin et al. (2018), Qebibo et al. (2024) |
| p.I962N | APC/MPC | de novo | Qebibo et al. (2024) |
| p.N1200S | APC/MPC | de novo | Kosmicki et al. (2017) |
| p.S1263A | APC | de novo | Qebibo et al. (2024) |
| p.I1412T | APC/ MPC | de novo | Qebibo et al. (2024) |
| p.M1531V | APC/MPC | de novo | Chemin et al. (2018), Qebibo et al. (2024) |
| p.G1534D | APC/ MPC | de novo | Qebibo et al. (2024) |
| p.R1715H | APC/MPC | inherited | Coutelier et al. (2015) |
| p.R1718G | APC | de novo | Riquet et al. (2023), Qebibo et al. (2024) |
| p.R1813W | APC | Congenital ataxia. Found in one patient, inherited from his mother, both also having a known pathogenic CACNA1A variant but with incomplete penetrance/expressivity | |
| p.V1835M | APC/MPC | inherited | A 2.5-year-old girl (in 2019) with developmental delay, microcephaly, and tremor (when scared/anxious). Exome sequencing revealed a pathogenic variant in MECP2, so she has Rett syndrome. She also has tremor. Her brain MRI at 1.5 years was normal; it did not show cerebellar atrophy |
| p.D2242N | APC | not known | Mild intellectual disability, ophthalmoplegia, and progressive ataxia, dysarthria, and dysphagia. He has developed prognathism. Brain MRI shows olivopontocerebellar atrophy |
The variants in bold-red are reported for the first time, with a brief clinical description of the related patients. Bold-underlined MPC indicates that the properties of these variants were preferentially obtained in MPC.