Early onset or syndromic epilepsy

Gene: RAB11B

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)

AD neurodevelopmental disorder with ataxic gait, absent speech and decreased cortical white matter - delayed and difficult walking, intellectual disability, absent speech and variable additional features including seizures. Lamers et al, 2017 - 5 unrelated patients similar features - 3 had childhood-onset epilepsy, 1 had a single seizures and 1 did not have anty seizures. Identify 2 recurrent de novo het missense variants - V22M and A68T. In vitro studies and molecular modelling done.

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
Neurodevelopmental disorder with ataxic gait absent speech and decreased cortical white matter, 617807

Publications

• 29106825

Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 5 unrelated cases, of which epileptic seizures were reported in three cases. Protein modeling suggested that both variants alter the GTP/GDP binding pocket and reveal that they both have localization patterns similar to inactive RAB11B (PMID 29106825).

Created: 26 Nov 2018, 2:27 p.m.

Comment on phenotypes: Added phenotype as suggested by external review and checked with OMIM

Created: 31 Oct 2018, 12:37 p.m.

Comment on mode of inheritance: updated MOI as suggested by external reviewer

Created: 31 Oct 2018, 12:36 p.m.

Green List (high evidence)

Seizures are described in 4 out of 5 individuals reported with this neurodevelopment disorder.

Created: 20 Aug 2018, 6:52 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, MIM#617807

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