Early onset or syndromic epilepsy
Gene: ARHGEF9
Marco et al, 2008 (17893116) female with a balanced paracentric inversion disrupting one allele of the ARHGEF9 gene between exons 1 and 3 who had EIEE8 - completely skewed X-inactivation in favour of the abnormal X chromosomeCreated: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Comment on mode of inheritance: Updated Mode of Inheritance from XLR to XLD based on Post-Webex review by Helen Lord.Created: 7 Sep 2019, 10:33 a.m. | Last Modified: 7 Sep 2019, 10:33 a.m.
Panel Version: 1.268
Mode of inheritance collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene is part of a subset where the mode of inheritance was re-reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy. No rating was included in the review, so I have uploaded a Green rating to match the original West Midlands, Oxford and Wessex GLH rating.Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262
Comment on mode of inheritance: OMIM lists XLR mode of inheritance for 'Epileptic encephalopathy, early infantile, 8' (MIM:300607). Gene2Phenotype lists hemizygous mode of inheritance (XLR) for EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 8.Created: 13 Aug 2019, 1:28 p.m. | Last Modified: 13 Aug 2019, 1:28 p.m.
Panel Version: 1.212
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
XLR EIEE8. Harvey et al, 2004 - boy with hyperkeplexia and epilepsy - het missense variant. Shimojima et al, 2011 - Japanese boy with X linked MR and epilepsy - LOF nonsense variant. Other missense/nonesense/splicing variants - 12 in total on HGMD pro. Also gross dels have a phenotype including epilepsy. Functional characterisaton of the R290H variant Papadopoulos et al, 2015.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Epileptic encephalopathy, early infantile, 8, 300607
Publications
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of inheritance: Captured from expert review.Created: 17 Dec 2015, 11:25 a.m.
Phenotypes for gene: ARHGEF9 were changed from Epileptic encephalopathy, early infantile, 8 300607 to Developmental and epileptic encephalopathy 8, OMIM:300607
Gene: arhgef9 has been classified as Green List (High Evidence).
Publications for gene: ARHGEF9 were set to 21633362; 15215304
Publications for gene: ARHGEF9 were set to
Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Mode of inheritance for gene: ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Source Wessex and West Midlands GLH was added to ARHGEF9.
Source NHS GMS was added to ARHGEF9.
Ellen McDonagh: Comment on mode of inheritance
Phenotypes for gene: ARHGEF9 were changed from to Epileptic encephalopathy, early infantile, 8 300607
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to ARHGEF9. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to ARHGEF9. Panel: Genetic Epilepsy Syndromes
ARHGEF9 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert,UKGTN,Radboud University Medical Center, Nijmegen
ARHGEF9 was created by Sarah Leigh