Hereditary haemorrhagic telangiectasia
Gene: EPHB4
On CGGL Royal Brompton HHT diagnostic panel. Pathogenic variants are a cause of Capillary malformation-arteriovenous malformation 2, a differential diagnosis of HHTCreated: 22 Sep 2019, 8:03 p.m. | Last Modified: 22 Sep 2019, 8:03 p.m.
Panel Version: 1.51
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
OMIM: 618196 Capillary malformation-arteriovenous malformation 2; 617300 Lymphatic malformation 7
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases and external expert review all support gene-disease association and relevance to this panel to rate gene as Green.Created: 27 Jun 2019, 10:53 a.m. | Last Modified: 27 Jun 2019, 10:53 a.m.
Panel Version: 1.49
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Hereditary haemorrhagic telangiectasia panelCreated: 27 Jun 2019, 10:48 a.m. | Last Modified: 27 Jun 2019, 10:48 a.m.
Panel Version: 1.47
Comment on publications: Added PMID: 30760892 from external reviewer to support upgrading of gene to GreenCreated: 27 Jun 2019, 10:46 a.m. | Last Modified: 27 Jun 2019, 10:46 a.m.
Panel Version: 1.46
Emerging as an HHT diagnostic mimic in patients sequenced through 100K with "HHT-like" telangiectasia. Note the syndrome is termed Capillary Malformation-Arteriovenous Malformation (CM-AVM2, PMID: 30760892) but a pathogenic EPHB4 variant was also identified in seven unrelated ENG/ACVRL1/SMAD4 negative cases presenting with features that might be considered suspicious of HHT (epistaxis, telangiectasia, [with significant differences in cutaneous presentation to HHT] and occasional cerebral malformations, PMID: 28687708).Created: 24 Jun 2019, 12:35 a.m. | Last Modified: 24 Jun 2019, 12:35 a.m.
Panel Version: 1.44
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
capillary malformation, epistaxis, telangiectasia, cerebral AVM
Publications
At least one family in 100k recruited under HHT has a mutation in this gene as it's an overlap condition. Consider whether to include with the GLH specialist group for GMS diagnostic analysis.
Sources: OtherCreated: 21 Jun 2019, 12:26 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Capillary malformation-arteriovenous malformation 2; 618196
Publications
Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2, 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2, OMIM:618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM
Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2, 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM
Gene: ephb4 has been classified as Green List (High Evidence).
Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM to Capillary malformation-arteriovenous malformation 2; 618196; Capillary malformation, epistaxis, telangiectasia, cerebral AVM
Phenotypes for gene: EPHB4 were changed from Capillary malformation-arteriovenous malformation 2; 618196 to Capillary malformation-arteriovenous malformation 2; 618196; capillary malformation, epistaxis, telangiectasia, cerebral AVM
Publications for gene: EPHB4 were set to 28687708; 28730721
Mode of inheritance for gene: EPHB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: ephb4 has been classified as Amber List (Moderate Evidence).
gene: EPHB4 was added gene: EPHB4 was added to Hereditary haemorrhagic telangiectasia. Sources: Other Mode of inheritance for gene: EPHB4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EPHB4 were set to 28687708; 28730721 Phenotypes for gene: EPHB4 were set to Capillary malformation-arteriovenous malformation 2; 618196 Penetrance for gene: EPHB4 were set to Incomplete Review for gene: EPHB4 was set to AMBER