Alpha 1 Mutations

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 diseases. 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. Genetic testing should be offered not only to patients at increased AATD risk , 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.

You can find two publications on this topic. (see links at the bottom of this page)

• 2021: Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency

• 2021: Known mutations at the cause of Alpha-1 Antitrypsin Deficiency an updated overview of SERPINA1 variation spectrum
   

A summary of the most common mutations and the AAT Serum levels for the most common combinations are shown in the table below.