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Updated: Aug 5, 2026
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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Community-Based SERPINA1 Genotyping in an Isolated Alpine Town Reveals Heterozygous Pi*Mheerlen Carriers:
Beatrice Ragnoli1,2, Carlotta Bertelegni3, Xheni Veselagu1
1Respiratory Unit, S. Andrea Hospital, 13100 Vercelli, Italy.
Biomedicines
|July 28, 2026
Summary
Alpha-1 antitrypsin deficiency (AATD) screening in an isolated Italian town found a 5.5% carrier rate, including rare variants. This suggests a local founder effect and highlights the importance of targeted genetic screening in unique populations.
Area of Science:
- Genetics and Genomics
- Population Health
- Rare Diseases
Background:
- Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed hereditary condition linked to lung and liver disease.
- Limited data exists on AATD prevalence in isolated populations outside Northern Europe.
- Investigating rare genotypes in secluded communities can reveal founder effects.
Purpose of the Study:
- To determine the prevalence of pathogenic SERPINA1 variants in the adult population of Ponte di Legno, an isolated Italian Alpine town.
- To investigate potential founder effects associated with rare AATD genotypes in this community.
Main Methods:
- A cross-sectional, community-based screening of adult residents without prior chronic respiratory diagnoses.
- Spirometry, serum AAT and CRP measurements, and buccal swab genotyping for 14 SERPINA1 variants using Luminex xMAP assay.
- Isoelectric focusing and Sanger sequencing were employed for further variant characterization when necessary.
Main Results:
- Ninety-one subjects were enrolled; 5.5% (5 individuals) carried pathogenic SERPINA1 variants.
- Detected variants included Pi*MS (1.1%), Pi*MZ (2.2%), and the rare Pi*Mheerlen (2.2%).
- AATD carriers exhibited significantly lower median serum AAT levels (100 mg/dL) compared to Pi*MM individuals (125 mg/dL).
Conclusions:
- The study identified a significant prevalence of AATD carriers in a geographically isolated Italian community.
- The presence of two Pi*Mheerlen variant carriers suggests a potential local founder effect.
- Targeted screening programs utilizing rare variant panels are valuable for uncovering genetic architectures in isolated populations.
