Hereditary haemorrhagic telangiectasia

Gene: ENG

Green List (high evidence)

On CGGL Royal Brompton HHT diagnostic panel. Extensive literature evidence

Created: 22 Sep 2019, 7:54 p.m. | Last Modified: 22 Sep 2019, 7:54 p.m.

Panel Version: 1.51

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
OMIM: 187300 Telangiectasia, hereditary hemorrhagic, type 1

Publications

• 9245986
• 7894484
• 15879500

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Please note for diagnostic applications that upstream promoter variants have been repeatedly described in this gene and diagnostic panels should cover at least to c.-130. The c.-127C>T variant is described in PMID 22192717, 21967607 , 28989145, others at -10 and -58 also described.

Created: 18 Jan 2019, 5:22 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Comment on phenotypes: added phenotypes suggested by expert reviewer

Created: 21 Jan 2019, 12:02 p.m.

Comment on publications: Added publications suggested by Ian Berry ( GMS Respiratory Specialist Test Group ) that support gene-disease association and rating of this gene to Green.

Created: 21 Jan 2019, noon

Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted ENG; Suggested initial gene rating: Green; Evidence for inclusion: OMIM HHT gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): Multiple promoter/UTR mutations, needs to be covered.

Created: 6 Dec 2018, 12:36 p.m.

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. At least 9 variants reported

Created: 12 Dec 2016, 11:39 a.m.

Comment on phenotypes: The following HPO terms provided by Claire Shovlin: Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707) Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574) Spinal arteriovenous malformation (HP:0002390). Additional phenotypes secondary to these diagnostic criteria.

Created: 12 Dec 2016, 11:39 a.m.

Green List (high evidence)

OMIM #187300 (HHT type 1, PMID 7894484)
Phenotypic differences to HHT type 2 due to ACVRL1, particularly frequency of hepatic, pulmonary and cerebral AVMs (PMID: 16155196), and lower prevalence of pulmonary arterial hypertension (PMID: 14684682)
ExAc Constraint metrics [http://biorxiv.org/content/early/2016/05/10/030338 ] identify ENG as a loss-of-function (LOF) intolerant gene, with better toleration of missense substitutions than ACVRL1 : Loss of function ENG expected 22.3, observed 2, pLI =0.99. Synonymous ENG expected number of ExAc variants123.3, observed 121, z=0.13. Missense ENG expected 235.9, observed 223, z=0.41 (contrast ACVRL1 expected 199.6, observed 132 z=2.34).

Created: 13 Nov 2016, 9:54 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epistaxis (HP:0000421); Nasal mucosa telangiectasia (HP:0000434); Lip telangiectasia (HP:0000214); Tongue telangiectasia (HP:0000227); Palate telangiectasia (HP:0002707) Finger pad telangiectasia (pulp not nail side); Gastrointestinal telangiectasia (HP:0002604); Arteriovenous malformation (HP:0100026); Cerebral arteriovenous malformation (HP:0002408); Pulmonary arteriovenous malformation (HP:0006548); Hepatic arteriovenous malformation (HP:0006574) Spinal arteriovenous malformation (HP:0002390). Additional phenotypes secondary to these diagnostic criteria.

Publications

• PMID: 7894484

Variants in this GENE are reported as part of current diagnostic practice