Early onset or syndromic epilepsy
Gene: MBD5
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
CHROMOSOME 2q23.1 DELETION SYNDROME.AD mental retardation 1 (MRD1) - see febrile seizures in infancy and non-febrile seizures later. Cytogenetically assoc with del or dup of 2q23.1 - in the deletions MBD5 is the smallest region of overlap. Molecularly - Wagenstaller et al, 2007 - 200kb del in MBD5- de novo. They also idenitifed 4 missense variants in MBD5 from chilsren with mental retardation - not present in 660 controls. Talkowski - identified MBD5 deletions in approx 0.18% of patiernts with autsim from 2 large cohorts (1786 and 2275 respectively) no deletions detected in 7878 controls. Found a missense change G79E in a highly conserved methyl CpG binding domain in 747 patients with autism spectrum disorder compared to controls - suggests alterations of MBD5 aredispose a risk to Autism spectrum dosorders. Carvill et al, 2013 - de nov het truncating mutation in a lady with severe mental retardation and epileptoic encephalopathy. Kleefstra et al 2012 - patient with some Kleefstra phenotype - found to have a fs mutation in MBD5.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
Mental retardation, 156200
Publications
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Mental retardation, autosomal dominant 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Mental retardation, autosomal dominant 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Mental retardation, autosomal dominant 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Mental retardation, autosomal dominant 1
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment when marking as ready: Possible DD gene, however all 4 reviewers agree this should be on the green list and report variants within this gene as part of current diagnostic practice.Created: 20 Jan 2016, 4:30 p.m.
Comment on mode of inheritance: Monoallelic confirmed on both G2P and OMIM. Not on the imprinted gene list.Created: 20 Jan 2016, 4:29 p.m.
Source Wessex and West Midlands GLH was added to MBD5.
Source NHS GMS was added to MBD5.
Ellen McDonagh: Comment on mode of inheritance
Victorian Clinical Genetics Services was added to MBD5. Panel: Genetic Epilepsy Syndromes
MBD5 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,UKGTN
MBD5 was created by Sarah Leigh