Early onset or syndromic epilepsy

Gene: MBD5

I don't know

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

Green List (high evidence)

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

• 23422940

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 1

Publications

• Wagenstaller et al (2007) Am J Hum Genet 81: 768-779

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 1

Publications

• Wagenstaller et al (2007) Am J Hum Genet 81: 768-779

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 1

Publications

• Wagenstaller et al (2007) Am J Hum Genet 81: 768-779

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Mental retardation, autosomal dominant 1

Publications

• Wagenstaller et al (2007) Am J Hum Genet 81: 768-779

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.