Pneumothorax - familial
Gene: SERPINA1
On Royal Brompton CGGL panel. AAT deficiency casues emphysema, with subsequent risk of pneumothorax.Created: 7 Nov 2019, 9:07 a.m. | Last Modified: 7 Nov 2019, 9:07 a.m.
Panel Version: 2.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
OMIM 613490 Emphysema/cirrhosis due to AAT deficiency
Publications
Variants in this GENE are reported as part of current diagnostic practice
Comment on phenotypes: added phenotype suggested by expert reviewerCreated: 7 Nov 2019, 3:44 p.m. | Last Modified: 7 Nov 2019, 3:44 p.m.
Panel Version: 2.12
From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: Agreed Green rating- suggest do not report carrier status.Created: 21 Jan 2019, 10:41 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: SERPINA1; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PCD gene or intersection of >2 panels; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none givenCreated: 6 Dec 2018, 2:37 p.m.
Comment on list classification: This gene was originally rated red, however in light of a new expert review and feedback from Helen Brittain (Genomics England Clinical Team), it is appropriate for this gene to be made green - variants in this gene cause emphysema, leading to bullae and therefore an increased risk of pneumothoraces.Created: 22 Sep 2017, 9:56 a.m.
Comment on publications: PMID: 27229674 - screened 40 primary spontaneous pneumothorax patients were screened for variants in 7 genes - no pathogenic variants were found in this gene in this cohort. PMID: 22544422 - a female case who was phenotyped (but not genotyped) as having null-type AAT deficiency who developed pneumothorax. PMID: 18619132 - a case of a male fighter pilot with early-onset pulmonary emphysema with bullae who developed spontaneous pneumothorax during in-flight combat training who had the PI ZZ genotype and decreased alpha-1 antitrypsin levels (full text article not available). PMID: 22215832 - twins who developed spontaneous familial pneumothorax were compound heterozygous for rare SERPINA1 alleles, one allele inherited from each parent.Created: 15 Sep 2017, 8:59 a.m.
Loss-of-function variants in SERPINA1 lead to alpha-1-antitrypsin deficiency, which can be complicated by severe, early-onset emphysema and/or cirrhosis of the liver. Patients with emphysema can develop spontaneous pneumothorax. Thus, individuals not yet diagnosed but with pathogenic genotype can present with spontaneous pneumothorax (for example, see PubMed ID: 18619132), and familial cases of this scenario have been reported (see 22215832).Created: 14 Sep 2017, 7:07 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
emphysema; cirrhosis; spontaneous familial pneumothorax; alpha-1-antitrypsin deficiency
Publications
Mutated in alpha1-antitrypsin (AAT) deficiency, most common single gene cause of emphysemaCreated: 8 Sep 2016, 3:22 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Emphysema due to AAT deficiency; Emphysema-cirrhosis, due to AAT deficiency
Publications
Phenotypes for gene: SERPINA1 were changed from Emphysema due to AAT deficiency; Emphysema-cirrhosis, due to AAT deficiency; Emphysema/cirrhosis due to AAT deficiency, 613490 to Emphysema due to AAT deficiency, OMIM:613490; Emphysema-cirrhosis, due to AAT deficiency, OMIM:613490
Phenotypes for gene: SERPINA1 were changed from Emphysema due to AAT deficiency; Emphysema-cirrhosis, due to AAT deficiency to Emphysema due to AAT deficiency; Emphysema-cirrhosis, due to AAT deficiency; Emphysema/cirrhosis due to AAT deficiency, 613490
Source NHS GMS was added to SERPINA1. Rating Changed from Green List (high evidence) to Green List (high evidence)
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for SERPINA1 were set to 22215832; 18619132; 27229674;22544422
Publications for SERPINA1 were set to 22215832; 18619132;27229674
Publications for SERPINA1 were set to 22215832;18619132
09/02/17 - Panel revised according to expert review, literature searches and clinical review.
This gene has been classified as Red List (Low Evidence).
This proposed gene was validated and added to this panel
SERPINA1 was created by [email protected]
SERPINA1 was added to Familial Pneumothoraxpanel. Sources: Expert list