What gene change causes alpha-1 antitrypsin deficiency?
Alpha-1 antitrypsin deficiency (AATD) is caused by changes, or mutations, in the SERPINA1 gene. These lead to very low level of the alpha-1 antitrypsin protein in the blood. Alpha-1 antitrypsin protein is made in the liver and usually protects the lungs. AATD is inherited in an autosomal recessive manner, so people with the condition have mutations in both copies of their SERPINA1 gene. There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD. AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually PI type "MZ").