Intellectual disability - microarray and sequencing
Gene: CACNA1AThe mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 5:50 p.m. | Last Modified: 30 Jan 2023, 5:50 p.m.
Panel Version: 4.53
Comment when marking as ready: De novo missense variants implicated in EIEE. Note that CACNA1A is responsible for other neurological phenotypes, including familial hemiplegic migraine caused by missense variants. However episodic ataxia / SCA6 are caused by a triplet repeat and therefore incidental findings of this nature would not be expected to be tiered.Created: 18 Dec 2017, 2:38 p.m.
Comment on mode of pathogenicity: De novo missense reported to dateCreated: 18 Dec 2017, 2:37 p.m.
PMIDs: 36063114; 34267336; 33445191; 27250579 all report biallelic CACNA1A variants in cases of Developmental and epileptic encephalopathy 42 (OMIM:617106), therefore the mode of inheritance should be changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.Created: 13 Sep 2022, 2:04 p.m. | Last Modified: 13 Sep 2022, 2:04 p.m.
Panel Version: 3.1707
The clinical features of epileptic encephalopathy, early infantile, 42 617106 include developmental delay and moderate to severe intellectual disability. Associated with phenotype in OMIM and as a possible G2P. Four different misense variants have been reported in five cases (including 2 sibs) of epileptic encephalopathy, early infantile, 42 617106. All were de novo except for the variant in the sibblings, which resulted from maternal somatic mosaicism.Created: 15 Dec 2017, 9:38 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Developmental and epileptic encephalopathy 42, OMIM:617106
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
EPILEPTIC ENCEPHALOPATHY
Publications
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_2_4_2017;in_gilissen_2014_known;in_omim_20150205_movement;in_UKGTN_v12 . Main mutation mechanism : All missense/in frameCreated: 27 Jul 2017, 5:14 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; gilissen_2014_known; omim_20150205_movement; UKGTN_v12; Nijmegen_ID_candidates; GEL_ID_red_20160217; neuro_20160418_strict; All missense/in frame. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 12:08 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
Mode of pathogenicity
Other
Tag Q3_22_MOI was removed from gene: CACNA1A.
Source NHS GMS was added to CACNA1A. Mode of inheritance for gene CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: CACNA1A were changed from Developemental and epileptic encephalopathy 42, OMIM:617106 to Developemental and epileptic encephalopathy 42, OMIM:617106; developmental and epileptic encephalopathy, 42, MONDO:0014917
Publications for gene: CACNA1A were set to 24896178; 27476654
Tag Q3_22_MOI tag was added to gene: CACNA1A.
Phenotypes for gene: CACNA1A were changed from Epileptic encephalopathy, early infantile, 42 617106; Episodic ataxia, type 2 108500; Migraine, familial hemiplegic, 1 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6 183086 to Developemental and epileptic encephalopathy 42, OMIM:617106
Source: Expert Review Red was removed from gene: CACNA1A
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
Expert Review Green was added to CACNA1A. Panel: Intellectual disability Model of inheritance for gene CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene CACNA1A was set to ['24896178', ' 27476654']
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
CACNA1A was added to Intellectual disabilitypanel. Sources: Expert Review Red
CACNA1A was created by ellenmcdonagh