Primary lymphoedema

Gene: ADAMTS3

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hennekam lymphangiectasia-lymphedema syndrome 3 618154

Publications

• 28985353
• 30450763

Comment on list classification: Associate with phenotype in OMIM, but not in Gen2Phen. At lease three variants in two cases, together with supportive functional studies (PMID 30450763).

Created: 24 Jul 2019, 10:25 a.m. | Last Modified: 24 Jul 2019, 10:27 a.m.

Panel Version: 1.86

I don't know

This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.

Created: 20 Feb 2019, 2:17 p.m.

Comment on list classification: Updated rating from Red to Amber as agreed with Helen Brittain and Anna De Burca: Insufficient evidence for diagnostic grade but features on St. George's Primary Lymphedema Disorders gene panel. Note that Prof. Sahar Mansour (St. George's hospital) confirmed via email thread that they have not seen cases.

Created: 29 Sep 2018, 3:09 p.m.

Comment on list classification: Kept rating as Red as currently insufficient cases for diagnostic grade (1 family in Brouillard et al. 2017).

Created: 18 Sep 2018, 12:13 p.m.

Added to panel as requested by Athina Ververi (GOSH) based on presence of ADAMTS3 on the St. George's Primary Lymphedema Disorders 15 Gene Panel.

Created: 18 Sep 2018, 12:11 p.m.

Mouse model for role of ADAMTS3 in lymphatic development is reported in PMID:26446156 (2016), with knockout mice exhibiting a massive lymphedema.

Created: 17 Sep 2018, 3:17 p.m.

PMID:28687807 (Jha et al., 2017) test a R565Q missense substitution in ADAMTS3 which was originally identified as a rare heterozygous polymoprhism in a lymphedema patient and in 6 unaffected members of the studied family as well as in 236 alleles in ExAC.

Created: 17 Sep 2018, 3:15 p.m.

PMID:28985353 (Brouillard et al. 2017) report biallelic (compound heterozygote) missense variants in ADAMTS3 in two siblings with Hennekam syndrome. The patients are Western European and non-consanguineous with no family history of lymphatic problems: c.503 T>C (p.Leu168Pro) was identified in affected siblings and unaffected father. c.872 T>C was recorded (p.Ile291Thr) in affected siblings and unaffected mother.

Created: 17 Sep 2018, 3:15 p.m.