Genetic epilepsy syndromesGene: CPA6
AR febrile seizures 11 (FEB11) and AD and AR familial temporal lobe epilepsy 5 (ELT5). In FEB11 - Salzmann et al, 2012 - 4 sibs born of consang Mroccan parents with highly variable manifestations of a seizure disorder. All 4 had febrile seizures and 1 laer developed temporal lobe epilepsy. Hom mutation in CPA6 - A270V. in vitro functional studies support LOF variant. ELT5 - Salzmann et al, 2012 - 3 unrelated caucasian patients with temporal lobe epilepsy - het mutation in CPA6 - G267R, In vitro functional studies support LOF variant. In one of these patients Sapio et al 2012 went on to idfentify a second het missense variant - Q207E, again expression studies support LOF. Sapio et al, 2012 - man with ETL5- seizures reported at aged 5 - het missense variant H196R no parental DNA. Functional studies were undertaken.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Epilepsy, familial temporal lobe, 5,614417; Febrile seizures, familial, 11,614418
Associated with phenotypes in OMIM and not in Gen2Phen. At least 4 variants identified: p.A270V as a homozygote in four siblings with Febrile seizures, familial, 11 (MIM 614418)(PMID:21922598), variant p.G267R was reported as a heterozygote in 3 unrelated cases of Epilepsy, familial temporal lobe, 5 (MIM 614417), of which one individual also carried a second CPA6 variant p.Q207E (PMID 23105115) and p.H196R was reported in a further case of Epilepsy, familial temporal lobe, 5 (MIM 614417). Supporting functional studies were also provided for variants p.A270V, p.G267R and p.H196R (PMID 23105115).
Created: 9 Apr 2018, 10:48 a.m.
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
In 4 sibs, born of consanguineous Moroccan parents, with febrile seizures-11 (MIM:614418), Salzmann et al. (2012, PMID:21922598) identified a homozygous 809C-T transition in exon 8 of the CPA6 gene resulting in a A270V substitution.
In 1 of the patients originally reported by Salzmann as having a heterozygous G267R mutation in CPA6, Sapio et al 2012 (PMID:23105115) identified a second heterozygous missense mutation (Q207E) in CPA6- this patient is associated with famililal temporal lobe epilepsy-5 (MIM:614417) in OMIM.
Created: 11 May 2017, 1:12 p.m.
Comment on list classification: Insufficient data
Created: 8 May 2016, 6:59 p.m.
Source Wessex and West Midlands GLH was added to CPA6.
Source NHS GMS was added to CPA6.
Richard Scott: Comment on list classification
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to CPA6. Panel: Genetic Epilepsy Syndromes
This gene has been classified as Green List (High Evidence).
Phenotypes for CPA6 were set to Epilepsy, familial temporal lobe, 5 614417 AR, AD; Febrile seizures, familial, 11 614418
Publications for CPA6 were set to 21922598; 23105115
Mode of inheritance for CPA6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
CPA6 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Red,Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services
CPA6 was created by Sarah Leigh