TREATMENTS &
RESEARCH

Search the
latest
treatment
information
here.

Dr. Huntley's
Diagnosis
Checklist

Have a symptom?
See what questions
a doctor would ask.

Next Prev

Diseases » Alpha 1-Antitrypsin Deficiency » Inheritance

Inheritance and Genetics of Alpha 1-Antitrypsin Deficiency

Alpha 1-Antitrypsin Deficiency Genetics: Book Excerpts

Alpha 1-Antitrypsin Deficiency - genetics - Alpha 1-Antitrypsin Deficiency

Alpha 1-Antitrypsin Deficiency: Genetics Information

Genetics of Alpha 1-Antitrypsin Deficiency: AAT inhibits elastase around normal tissue. Deficiency is caused by mutations in the SERPINA1 gene, located on chromosome 14. This gene has many different versions (alleles) that produce different amounts of AAT. The M allele produces normal levels of the AAT protein, the S allele produces moderately low levels, and the Z allele produces very low levels.

The alleles are expressed in a codominant manner --- that means that a person with MZ has levels of AAT that are between the levels of those people who have alleles MM or ZZ.

Individuals who have at least one normal allele (MZ or MS) or two copies of S (SS) usually produce enough AAT to protect the lungs but do have an increased risk of lung disease. The risk is particularly high if they smoke. Individuals who inherit the Z allele from each parent (ZZ) have very low AAT and are at a higher risk of developing emphysema and liver disease.

There are over 70 known mutations that occur at the SERPINA1 gene. A common mutation that creates the Z allele involves a switch in amino acids --- glutamic acid is replaced by lysine at position 342 (Glu342Lys). The resulting AAT protein cannot fold properly. This hinders its secretion from the liver (which makes AAT) into the bloodstream (which transports AAT to the lungs). The accumulation of AAT complexes can damage the liver, whereas the lack of AAT fails to stop the destruction of lung tissue. (Source: Genes and Disease by the National Center for Biotechnology)

About inheritance and genetics:

Inheritance of Alpha 1-Antitrypsin Deficiency refers to whether the condition is inherited from your parents or "runs" in families. The level of inheritance of a condition depends on how important genetics are to the disease. Strongly genetic diseases are usually inherited, partially genetic diseases are sometimes inherited, and non-genetic diseases are not inherited. For general information, see Introduction to Genetics.