Alpha1-antitrypsin deficiency in Greece: Focus on rare variants

Area of Science:

• Genetics
• Pulmonology
• Biochemistry

Background:

• Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder.
• Pathogenic mutations for AATD are expanding beyond common PI*Z and PI*S variants.
• Understanding rare variants is crucial for comprehensive diagnosis and management.

Purpose of the Study:

• To investigate the genotype and clinical profile of Greek patients with AATD.
• To identify and characterize rare AATD variants in the Greek population.
• To expand knowledge on the geographical distribution of rare AATD variants in Europe.

Main Methods:

• Symptomatic adult patients with early-emphysema and low AAT levels were enrolled.
• Genetic analysis was performed using Luminex genotyping and gene sequencing.
• Samples were analyzed at the AAT Laboratory in Marburg, Germany.

Main Results:

• 45 adults were included, with 38 having pathogenic variants.
• A multiplicity of rare AATD variants and combinations were identified in two-thirds of patients.
• Significant differences in AAT levels were observed between genotypes (p=0.002).

Conclusions:

• Genotyping in Greece revealed diverse rare AATD variants and combinations, including unique ones.
• Gene sequencing proved necessary for accurate genetic diagnosis of AATD.
• Detection of rare genotypes can inform personalized preventive and therapeutic strategies for AATD.