Hereditary haemorrhagic telangiectasia

Gene: RASA1

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 11:07 a.m. | Last Modified: 8 Mar 2022, 11:07 a.m.

Panel Version: 2.13

Green List (high evidence)

Comment on list classification: This gene will be flagged for review at the date of next GMS panel update (added 'for-review' tag).

Given the phenotypic overlap with HHT, these patients are likely to benefit from inclusion of RASA1 on a HHT panel, aiding detection rate and accurate diagnosis. Therefore, a rating upgrade from Red to Green should be considered.

Created: 2 Oct 2020, 2:49 p.m. | Last Modified: 2 Oct 2020, 2:49 p.m.

Panel Version: 2.5

PMID: 27081547 (2015) - In two individuals who were clinically suspected to have HHT due to epistaxis and dermal lesions such as telangiectases, sequencing revealed different heterozygous variants in RASA1. One variant was said to segregate in two additional family members, but no information regarding segregation of the other variant is provided.

PMID: 29891884 (2018) - At least six individuals with a RASA1 variant who were initially suspected for HHT - at least three of whom were genetically tested for this clinical indication but yielded negative results.

PMID: 32900839 (2020) - Two unrelated cases of RASA1-related capillary malformation-arteriovenous malformation syndrome mimicking hereditary haemorrhagic telangiectasia. Features that are typically characteristic of HHT included cerebral AVMs, epistaxi, and mucocutaneous and hepatic vascular lesions in a 28-year-old male; and cyanosis, mucocutaneous telangiectasias, pulmonary and hepatic AVMs in a 9-year-old girl. Both were suspected for HHT but genetic testing did not detect any variants in HHT-related genes, and instead revealed LoF variants in RASA1. Segregation analysis confirmed de novo occurrence in the male; however, the variant found in the female was also identified in three non-symptomatic relatives.

Created: 2 Oct 2020, 2:39 p.m. | Last Modified: 2 Oct 2020, 2:39 p.m.

Panel Version: 2.4

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

Phenotypes
Capillary malformation-arteriovenous malformation 1, 608354

Publications

• 27081547
• 29891884
• 32900839

Green List (high evidence)

Consider upgrading due to possible phenotypic overlap along similar lines to EPHB4.

Created: 27 Jul 2020, 4:33 a.m. | Last Modified: 27 Jul 2020, 4:33 a.m.

Panel Version: 2.4

Comment on list classification: Demoted to red due to expert input regarding the phenotype not being relevant to this panel.

Created: 14 Dec 2016, 9:56 a.m.

Comment when marking as ready: Phenotypes not relevant to this panel according to expert reviewer Claire Shovlin (Imperial College London)

Created: 13 Dec 2016, 2:08 p.m.

Comment on phenotypes: Also associated with Parkes Weber syndrome, 608355; Basal cell carcinoma, somatic, 605462

Created: 13 Dec 2016, 2:07 p.m.

Comment on phenotypes: Also associated with Parkes Weber syndrome 608355 and Basal cell carcinoma, somatic 605462

Created: 13 Dec 2016, 2:04 p.m.

Comment when marking as ready: Associated with phenotypes in OMIM and as a confirmed Developmental Disorder Gene / G2P. At least three variants reported in Capillary malformation-arteriovenous malformation 608354

Created: 13 Dec 2016, 2:01 p.m.

Comment on phenotypes: Also associated with Basal cell carcinoma, somatic 605462

Created: 12 Dec 2016, 4:23 p.m.

Red List (low evidence)

To the best of my knowledge, at present the RASA1 phenotypic spectrum is distinct from the HHT spectrum, displaying different types of telangiectasia and different patterns of arteriovenous malformations (PMID: 18446851) but this may change in the future.

Created: 13 Nov 2016, 11:17 p.m.