PMID- 34408833
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210903
IS  - 2040-6223 (Print)
IS  - 2040-6231 (Electronic)
IS  - 2040-6223 (Linking)
VI  - 12_suppl
DP  - 2021
TI  - Variants of SERPINA1 and the increasing complexity of testing for alpha-1 
      antitrypsin deficiency.
PG  - 20406223211015954
LID - 10.1177/20406223211015954 [doi]
LID - 20406223211015954
AB  - Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the SERPINA1 
      gene, which encodes the alpha-1 antitrypsin (AAT) protein. Currently, over 200 
      SERPINA1 variants have been identified, many of which cause the quantitative 
      and/or qualitative changes in AAT responsible for AATD-associated lung and liver 
      disease. The types of these pathogenic mutations are varied, often resulting in 
      misfolding, or truncating of the AAT amino acid sequence, and improvements in 
      sequencing technology are helping to identify known and novel genetic variants. 
      However, due to the diversity and novelty of rare variants, the clinical 
      significance of many is largely unknown. There is, therefore, a lack of guidance 
      on how patients should be monitored and treated when the clinical significance of 
      their variant combination is unclear or variable. Nevertheless, it is important 
      that physicians understand the advantages and disadvantages of the different 
      testing methodologies available to diagnose AATD. Owing to the autosomal 
      inheritance of the genetic mutations responsible for AATD, genetic testing should 
      be offered not only to patients at increased AATD risk (e.g. patients with 
      chronic obstructive pulmonary disease), but also to relatives of those with an 
      abnormal result. Genetic counseling may help patients and family members 
      understand the possible outcomes of testing and the implications for the family. 
      While stress/anxiety can arise from genetic diagnosis or confirmation of carrier 
      status, there can be positive consequences to genetic testing, including improved 
      lifestyle choices, directed medical care, and empowered family planning. As 
      genetic testing technology grows and becomes more popular, testing without 
      physician referral is becoming more prevalent, irrespective of the availability 
      of genetic counseling. Therefore, the Alpha-1 Foundation offers genetic 
      counseling, as well as other support and educational material, for patients with 
      AATD, as well as their families and physicians, to help improve the understanding 
      of potential benefits and consequences of genetic testing.
CI  - (c) The Author(s), 2021.
FAU - Foil, Kimberly E
AU  - Foil KE
AD  - Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical 
      University of South Carolina, Charleston, SC 29425, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210729
PL  - United States
TA  - Ther Adv Chronic Dis
JT  - Therapeutic advances in chronic disease
JID - 101532140
PMC - PMC8367212
OTO - NOTNLM
OT  - SERPINA1
OT  - alpha-1 antitrypsin
OT  - alpha-1 antitrypsin deficiency
OT  - genetic counseling
OT  - rare variants
OT  - testing
COIS- Conflict of interest statement: The author declares that there is no conflict of 
      interest.
EDAT- 2021/08/20 06:00
MHDA- 2021/08/20 06:01
PMCR- 2021/07/29
CRDT- 2021/08/19 06:41
PHST- 2020/10/16 00:00 [received]
PHST- 2021/04/20 00:00 [accepted]
PHST- 2021/08/19 06:41 [entrez]
PHST- 2021/08/20 06:00 [pubmed]
PHST- 2021/08/20 06:01 [medline]
PHST- 2021/07/29 00:00 [pmc-release]
AID - 10.1177_20406223211015954 [pii]
AID - 10.1177/20406223211015954 [doi]
PST - epublish
SO  - Ther Adv Chronic Dis. 2021 Jul 29;12_suppl:20406223211015954. doi: 
      10.1177/20406223211015954. eCollection 2021.