Early onset or syndromic epilepsy

Gene: ARHGEF9

Green List (high evidence)

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 chromosome

Created: 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)

I don't know

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

Green List (high evidence)

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

• 21633362
• 15215304

Green List (high evidence)

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

Green List (high evidence)

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

Green List (high evidence)

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

Green List (high evidence)

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.