Identification of a novel alpha1-antitrypsin variant

Area of Science:

• Genetics
• Pulmonology
• Hepatology

Background:

• Alpha-1-antitrypsin deficiency (A1ATD) is a genetic disorder caused by SERPINA1 mutations.
• It leads to reduced serum protease inhibitor activity, increasing risk for emphysema and liver disease.
• Common genotypes include PIZZ and PISZ, but deficient or null alleles also cause disease.

Observation:

• A 64-year-old woman presented with dyspnea on exertion, bilateral bronchiectasis, and moderate panacinar emphysema.
• Pulmonary function tests (PFTs) were subnormal with noted hypoxemia.
• Quantitative analysis revealed severe Alpha-1-antitrypsin deficiency.

Findings:

• DNA sequencing identified compound heterozygosity for the PIZ variant and a novel missense variant, p.Phe232Leu (p.Phe208Leu).
• This novel variant contributes to the severe Alpha-1-antitrypsin deficiency observed.
• No specific treatment was initiated due to normal PFTs at diagnosis.

Implications:

• The identification of novel SERPINA1 variants expands the understanding of A1ATD genetic basis.
• Early diagnosis through genetic testing is crucial for managing A1ATD.
• Close monitoring of pulmonary and hepatic health is recommended for patients with A1ATD.