Thoracic aortic aneurysm or dissection

Gene: ADAMTSL4

Comment on list classification: Promoted from Red to Green based on expert review from Ellen Thomas (Genomics England Curator).

Created: 13 Jan 2020, 11:04 a.m. | Last Modified: 13 Jan 2020, 11:04 a.m.

Panel Version: 1.111

Green List (high evidence)

Promote to green for 100k FTAAD panel as ectopia lentis could be recruited under this disorder category in the project so there is an argument to include this due to phenotypic overlap.

Created: 10 Jan 2020, 2:07 p.m. | Last Modified: 10 Jan 2020, 2:07 p.m.

Panel Version: 1.110

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Ectopia lentis et pupillae; Ectopia lentis, isolated, autosomal recessive

Comment on list classification: This gene has been added to this panel initially as Red, and is awaiting clinical judgement as to whether this should be included diagnostically on this panel.

Created: 23 Apr 2019, 3:21 p.m.

Green List (high evidence)

ADAMTSL4 is not currently available as a green gene on any panel. It is red in both the Craniosynostosis and Cataracts panels. In OMIM it is associated with Ectopia lentis (isolated and et pupillae).
There may be an argument for including this on the panel as a differential diagnosis for Marfan syndrome (although there are no cardiac features), particularly as the test for Marfan syndrome has been amalgamted with TAAD in the Test directory.
The gene is included in the Wessex UKGTN TAAD panel and to date we have identified six homozygous cases of c.767_786del and one compound heterozygote. Four were referred for Marfan syndrome and specifically requested FBN1 testing.
Sources: UKGTN

Created: 20 Feb 2019, 10:51 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal