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| Intellectual disability v2.1012 | CACNA1B | Louise Daugherty Added comment: Comment on phenotypes: added OMIM MIM id | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.1012 | CACNA1B | Louise Daugherty Phenotypes for gene: CACNA1B were changed from Progressive Epilepsy-Dyskinesia; Seizures; Abnormality of movement; Intellectual disability; Developmental regression; Global developmental delay to Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, 618497; Progressive Epilepsy-Dyskinesia; Seizures; Abnormality of movement; Intellectual disability; Developmental regression; Global developmental delay | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.978 | CACNA1B |
Catherine Snow Source Expert Review was added to CACNA1B. Added phenotypes Global developmental delay; Seizures; Intellectual disability; Abnormality of movement; Developmental regression for gene: CACNA1B Publications for gene CACNA1B were changed from 30982612; 25296916 to 26157024; 30982612 |
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| Intellectual disability v2.930 | CACNA1B | Louise Daugherty Classified gene: CACNA1B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.930 | CACNA1B | Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team: appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.930 | CACNA1B | Louise Daugherty Gene: cacna1b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.929 | CACNA1B | Louise Daugherty Added comment: Comment on phenotypes: added Progressive Epilepsy-Dyskinesia from PMID:30982612. gene-phenotype currently not listed in OMIM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.929 | CACNA1B | Louise Daugherty Phenotypes for gene: CACNA1B were changed from Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement to Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement; Progressive Epilepsy-Dyskinesia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.928 | CACNA1B | Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.928 | CACNA1B | Louise Daugherty Publications for gene: CACNA1B were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Intellectual disability v2.800 | CACNA1B |
Konstantinos Varvagiannis gene: CACNA1B was added gene: CACNA1B was added to Intellectual disability. Sources: Literature Mode of inheritance for gene: CACNA1B was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CACNA1B were set to Global developmental delay; Developmental regression; Seizures; Intellectual disability; Abnormality of movement Penetrance for gene: CACNA1B were set to Complete Review for gene: CACNA1B was set to GREEN Added comment: Gorman et al. (2019 - doi.org/10.1016/j.ajhg.2019.03.005) report on 6 individuals from 3 unrelated families, with biallelic LoF CACNA1B variants. The phenotype corresponds to a developmental epilepic encephalopathy with hyperkinetic movement disorder (ID was a universal feature, DD and/or regression occurred prior to the onset of seizures in several individuals) . CACNA1B encodes calcium channel, voltage-dependent N type, α-1B subunit (Ca v2.2). As commented by the authors, Ca v2.1 and v2.2 are important for SNARE-mediated release of neurotransmitters through modulation of Ca+2 levels. In addition, Ca v2.2 has been postulated to have a role in synaptic plasticity, synaptogenesis, migration of immature neurons, etc. It is thought to have a crucial role in neurotransmission in the early postnatal period (Ca v2.2 channels are subsequently replaced by Ca v2.1 in mature synapses within the thalamus, cerebellum and auditory brainstem). Knockout mice display neurodevelopmental abnormalities including impaired locomotor activity and memory impairment (all ref. cited within the article). 3 sibs, born to 1st cousin parents, harbored p.Leu1222Argfs*29 (NM_000718.4:c.3665del) in the homozygous state. One additional individual was homozygous for p.Arg383*. Compound heterozygosity for a frameshift and a splicing variant (p,Gly1192Cysfs* and c.4857+1G>C) was identified in 2 sibs from a 3rd family. Expression/functional studies have not been performed for any of the variants reported. In OMIM, monoallelic CACNA1B pathogenic variants are associated with ?Dystonia 23 (MIM 614860) based on the identification of a heterozygous missense (R1389H) mutation in members of a Dutch with myoclonus-dystonia syndrome (Groen et al. 2015 - PMID: 25296916). As a result, this gene can be considered for inclusion in the epilepsy and ID panels as green (or amber). Sources: Literature |
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