Arthrogryposis
Gene: CACNA1E
De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias: Helbig et al identified 30 unrelated individuals with missense variants in CACNA1E. 13/30 (43%) affected individuals had congenital joint contractures ranging from isolated talipes equinovarus to arthrogryposis multiplex congenita.Functional analysis of several missense variants revealed highly consistent gain-of-function effects, characterized by facilitated voltage-dependent activation, slowed inactivation, and increased current density.Created: 27 Nov 2019, 4:50 p.m. | Last Modified: 27 Nov 2019, 4:50 p.m.
Panel Version: 2.84
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epileptic encephalopathy, early infantile, 69
Publications
Mode of pathogenicity
Other
Comment on list classification: Updated rating of CACNA1E from Amber to Green following review and confirmation from Zerin Hyder (Genomics England Clinical Team).Created: 27 Nov 2019, 9:02 p.m. | Last Modified: 27 Nov 2019, 9:02 p.m.
Panel Version: 2.86
Comment on mode of pathogenicity: Set Mode of pathogenicity to 'Other' following Zerin Hyder's review about G.O.F variants in PMID:30343943 (Helbig et al., 2018).Created: 27 Nov 2019, 9:01 p.m. | Last Modified: 27 Nov 2019, 9:01 p.m.
Panel Version: 2.85
Comment on list classification: Promoted to Amber awaiting clinical review: PMID:30343943 (Helbig et al., 2018) identified 30 unrelated individuals with missense variants in CACNA1E. 13/30 (43%) affected individuals had congenital joint contractures ranging from isolated talipes equinovarus to arthrogryposis multiplex congenita.Created: 26 Nov 2019, 9:56 p.m. | Last Modified: 26 Nov 2019, 9:56 p.m.
Panel Version: 2.76
Added to Arthrogryposis panel as suggested by Zerin Hyder (Genomics England Clinical Team).Created: 26 Nov 2019, 3:16 p.m. | Last Modified: 26 Nov 2019, 3:16 p.m.
Panel Version: 2.64
Gene: cacna1e has been classified as Green List (High Evidence).
Mode of pathogenicity for gene: CACNA1E was changed from to Other
Gene: cacna1e has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: CACNA1E were changed from Epileptic encephalopathy, early infantile, 69, 618285 to Epileptic encephalopathy, early infantile, 69, 618285; congenital joint contractures
Mode of inheritance for gene: CACNA1E was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CACNA1E were changed from to Epileptic encephalopathy, early infantile, 69, 618285
Publications for gene: CACNA1E were set to
gene: CACNA1E was added gene: CACNA1E was added to Arthrogryposis. Sources: Expert Review Red Mode of inheritance for gene: CACNA1E was set to