Description of alpha-1-antitrypsin deficiency associated with PI*Q0ourém allele in La Palma Island (Spain) and a genotyping assay for its detection.

By analysis of a case of discrepancy between serum alpha-1-antitrypsin (AAT) level and genotype for the most common defective alleles associated with AAT deficiency (PIS and PIZ), a patient carrying the allele PIQ0ourém has been identified for the first time outside of Portugal. This null allele has been implicated in cases of severe pulmonary emphysema. After developing a clinical assay for detection of c.1130insT mutation, based on fluorescent probes (HybProbe®), another 4 carriers of PIQ0ourém allele were identified among 43 patients with abnormally low serum AAT levels based on their genotypes for PIS and PIZ alleles. Since 4 out 5 cases are from the same locality (La Palma Island, Spain), it is advisable to conduct genetic analyses of affected families and, possibly, a focused population screening.