Early onset or syndromic epilepsy
Gene: BRAF
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
AD CFC, AD Noonan and AD Leopard syndromes - all of which have phenotypic overlap. Leopard - Sarkozy et al, 2009 - patient whose features included seizures - de novo het missese varint - same variant identified in 2 patients with CFC1. Armour and Allanson 2008 - clinical features of 38 patients with genetically confirmed CFC syndrome - seizures in 49%. Gene will also be on Noonans panel seizures reported at aignificant rate.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Adenocarcinoma of lung, somatic 211980; Cardiofaciocutaneous syndrome, 115150; Colorectal cancer, somatic; LEOPARD syndrome, 613707; Melanoma, malignant, somatic; Nonsmall cell lung cancer, somatic; Noonan syndrome, 613706
Publications
Comment when marking as ready: Associated with relevant phenotypes in OMIM and as confirmed Gen2Phen gene for Cardiofaciocutaneous syndrome 115150 & LEOPARD syndrome 3 613707. PMID 18039946 reported seizures in around half of their genetically confirmed Cardiofaciocutaneous syndrome 115150 cases (n=38) and PMID 19206169 reports 11 variants in 9 cases of Cardiofaciocutaneous syndrome 115150, 2 cases of Noonan syndrome 7 613706 and one case of LEOPARD syndrome 3 613707.Created: 12 Nov 2018, 4:53 p.m.
Comment on mode of pathogenicity: Activating variants responsible for phenotypeCreated: 12 Nov 2018, 4:20 p.m.
Seizures are a common feature of CFC syndrome.Created: 8 Aug 2018, 1:25 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Cardiofaciocutaneous syndrome, MIM#115150
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to BRAF.
Source NHS GMS was added to BRAF.
Zornitza Stark: Seizures are a common feature
Gene: braf has been classified as Green List (High Evidence).
Gene: braf has been classified as Green List (High Evidence).
Phenotypes for gene: BRAF were changed from Cardiofaciocutaneous syndrome 115150; LEOPARD syndrome 3 613707 to Cardiofaciocutaneous syndrome 115150; Noonan syndrome 7 613706; LEOPARD syndrome 3 613707
Mode of pathogenicity for gene: BRAF was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: BRAF were set to
Phenotypes for gene: BRAF were changed from to Cardiofaciocutaneous syndrome 115150; LEOPARD syndrome 3 613707
Mode of inheritance for gene: BRAF was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Expert Review Amber was added to BRAF. Panel: Genetic Epilepsy Syndromes
BRAF was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
BRAF was created by Sarah Leigh