A New SERPINA-1 Missense Mutation Associated with Alpha-1 Antitrypsin Deficiency and Bronchiectasis

Area of Science:

• Genetics
• Pulmonology
• Biochemistry

Background:

• Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder primarily caused by SERPINA1 gene mutations.
• It leads to reduced serum protease inhibitor activity, increasing susceptibility to emphysema.
• Commonly associated genotypes include ZZ and SZ, with rare alleles also contributing.

Observation:

• A 52-year-old woman presented with bronchiectasis and decreased alpha-1 globin band on electrophoresis.
• Her alpha-1 antitrypsin (AAT) levels were below normal (78 mg/dl).
• Standard S and Z mutations were absent.

Findings:

• Sequencing revealed a novel heterozygous missense variant, Ile74Asn (c.221T>A), in the SERPINA1 gene.
• This variant occurred on an M3 allele (Glu400Asp) in exon 2.
• The novel mutation likely results in a dysfunctional AAT protein.

Implications:

• This case expands the spectrum of SERPINA1 mutations associated with AATD.
• The identification of Ile74Asn offers a new genetic marker for AATD.
• The association with bronchiectasis, in the absence of emphysema, suggests diverse clinical presentations of AATD.