Early onset or syndromic epilepsy
Gene: RANBP2
p.Thr585Met gnomAD frequency (1/245874) and seen in 9 of 15 families suspected of having familial or recurrent acute necrotizing encephalopathy. Potential risk factor. AD susceptibility to acute infection induced encephalopathy 3 (IIAE3). Molecular genetics on OMIM - Neilson et al 2009 - suggest that mutations in RANBP2 gene predispose to acute necrotising encephalopathy following febrile illness - but by themselves are insufficient to make the phenotype fully penetrant and additional genetic and environmental factors are required. In addition 4 more affected famiies did not carry RANBP2 mutationsCreated: 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
{Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033
Publications
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: Amber.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Demoted RANBP2 from Green to Amber following review by Zornitza Stark and agreement from Helen Brittain (Genomics England clinical team). Recent papers report patients with symptoms (including seizures) after a viral illness (PMID:30796099, PMID:28336122, PMID:25128471). However, listed as a susceptibility locus in OMIM, and papers report incomplete penetrance: variant present in asymptomatic maternal grandmother in PMID:30796099 and in the father in PMID:28336122. Therefore further information (e.g. on penetrance) is required for a clear gene:disease association.Created: 25 Jul 2019, 3:28 p.m. | Last Modified: 25 Jul 2019, 3:29 p.m.
Panel Version: 1.181
We consider this a susceptibility gene, rather than a true monogenic condition, and as such would only analyse when specifically indicated based on presenting features and report only variants where increased risk is clearly established.Created: 20 Aug 2018, 10:15 a.m.
The condition associated with RANBP2 is reported in gene reviews and other publications as monoallelic with incomplete penetrance
https://www.ncbi.nlm.nih.gov/books/NBK258641/
PMID: 25522933
PMID: 19118815Created: 30 Sep 2017, 8:57 a.m.
Comment on publications: publications suggested by Andrea Haworth (ACGS, Congenica) as evidence for autosomal incomplete penetranceCreated: 9 Oct 2017, 10:42 a.m.
Comment on "Treatable" tag: Early diagnosis could allow potentially beneficial measures, such as ensuring up-to-date immunization status (eg, against influenza), though full protection against all inciting agents would not be possibleCreated: 20 Mar 2017, 11:22 a.m.
Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.Created: 20 Mar 2017, 11:21 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
{Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033
Source Wessex and West Midlands GLH was added to RANBP2.
Source NHS GMS was added to RANBP2.
Gene: ranbp2 has been classified as Amber List (Moderate Evidence).
Sarah Leigh: Inclusion of this as a green g
Phenotypes for gene: RANBP2 were changed from {Encephalopathy, acute, infection-induced, 3, susceptibility to} to {Encephalopathy, acute, infection-induced, 3, susceptibility to} 608033
RANBP2 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review,Expert Review Green
RANBP2 was created by Sarah Leigh