Hereditary haemorrhagic telangiectasia
Gene: RASA1The 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
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
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, 605462Created: 13 Dec 2016, 2:07 p.m.
Comment on phenotypes: Also associated with Parkes Weber syndrome 608355 and Basal cell carcinoma, somatic 605462Created: 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 608354Created: 13 Dec 2016, 2:01 p.m.
Comment on phenotypes: Also associated with Basal cell carcinoma, somatic 605462Created: 12 Dec 2016, 4:23 p.m.
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.
Tag for-review was removed from gene: RASA1.
Source Expert Review Green was added to RASA1. Rating Changed from Red List (low evidence) to Green List (high evidence)
Tag for-review tag was added to gene: RASA1.
Publications for gene: RASA1 were set to 18446851; 27081547
Gene: rasa1 has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Phenotypes for RASA1 were set to Capillary malformation-arteriovenous malformation 608354
Phenotypes for RASA1 were set to Hereditary hemorrhagic telangiectasia (HHT)
This gene has been classified as Red List (Low Evidence).
Promoted to V1 (12th December 2016)
Mode of inheritance for RASA1 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
RASA1 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services
Phenotypes for RASA1 were set to Parkes Weber syndrome 608355; Hereditary hemorrhagic telangiectasia (HHT)
Publications for RASA1 were set to 18446851; 27081547
Publications for RASA1 were set to 18446851
RASA1 was added to Hereditary haemorrhagic telangiectasiapanel. Sources: Emory Genetics Laboratory
RASA1 was created by ellenmcdonagh