Pneumothorax - familial
Gene: SMAD2
Missense variants reported in Loeys-Dietz syndrome, for which there are sufficient cases. Increased SMAD2 expression noted in bullae from patients who have had pneumothoraces. I cannot find clear evidence of individuals with SMAD2 pathogenic variants who have had pneumothoraces, although there are relatively small numbers of cases reported.Created: 18 Jan 2019, 2:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Loeys-Dietz syndrome
Publications
Mode of pathogenicity
Other
October 2019: Gene flagged up for further discussion by Respiratory Test Group regarding the inclusion of genes associated with Loeys-Dietz syndrome and classical EDS. However, no additional feedback was received, so gene will not be upgraded to Green as inclusion on this panel remains unclear. COL5A1, SMAD2 and SMAD3 are rated Green on the R101 Ehlers Danlos syndromes panel https://panelapp.genomicsengland.co.uk/panels/53/Created: 5 Nov 2019, 2:56 p.m. | Last Modified: 5 Nov 2019, 2:56 p.m.
Panel Version: 1.18
Comment on phenotypes: added phenotype as suggested by clinical teamCreated: 21 Jan 2019, 12:15 p.m.
Comment on publications: Added publications suggested by expert clinical review that support Loeys-Dietz syndrome; pneumothorax a common feature.Created: 21 Jan 2019, 12:14 p.m.
Comment on mode of inheritance: added MOI from reviewCreated: 21 Jan 2019, 12:12 p.m.
Comment on list classification: changed to Amber from Red - awaiting confirmation from GMS Respiratory Specialist Test Group- is pneumothorax part of the phenotype for LDS caused by variants in SMAD2Created: 21 Jan 2019, 12:12 p.m.
From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: Loeys-Dietz syndrome - is pneumothorax part of the phenotype for LDS caused by variants in these genes? Specialist group to contact Stefan Marciniak/Bart Loeys to confirm thisCreated: 21 Jan 2019, 10:39 a.m.
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: SMAD2; Suggested initial gene rating: Green; Evidence for inclusion: Loeys-Dietz syndrome; pneumothorax a common feature. New gene not on PanelApp, see PMID 29392890 & 26247899.; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none givenCreated: 6 Dec 2018, 2:37 p.m.
Phenotypes for gene: SMAD2 were changed from Loeys-Dietz syndrome to Loeys-Dietz syndrome,MONDO:0018954
Phenotypes for gene: SMAD2 were changed from to Loeys-Dietz syndrome
Publications for gene: SMAD2 were set to
Mode of pathogenicity for gene: SMAD2 was changed from to Other
Mode of inheritance for gene: SMAD2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: smad2 has been classified as Amber List (Moderate Evidence).
gene: SMAD2 was added gene: SMAD2 was added to Pneumothorax - familial. Sources: NHS GMS Mode of inheritance for gene: SMAD2 was set to