Early onset or syndromic epilepsy
Gene: RAB11B
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 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
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 OMIMCreated: 31 Oct 2018, 12:37 p.m.
Comment on mode of inheritance: updated MOI as suggested by external reviewerCreated: 31 Oct 2018, 12:36 p.m.
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
Phenotypes for gene: RAB11B were changed from Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, 617807 to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, OMIM:617807
Source Wessex and West Midlands GLH was added to RAB11B.
Source NHS GMS was added to RAB11B.
Zornitza Stark: Seizures are described in 4 ou
Gene: rab11b has been classified as Green List (High Evidence).
Publications for gene: RAB11B were set to
Gene: rab11b has been classified as Green List (High Evidence).
Phenotypes for gene: RAB11B were changed from to Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter, 617807
Mode of inheritance for gene: RAB11B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Expert Review Amber was added to RAB11B. Panel: Genetic Epilepsy Syndromes
RAB11B was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
RAB11B was created by Sarah Leigh