Description of Alpha-1-Antitrypsin Deficiency Associated With PI*Q0ourém Allele in La Palma Island (Spain) and a Genotyping Assay for Detection☆

Abstract 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 ( PI*S and PI*Z ), a patient carrying the allele PI*Q0 ourem 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 PI*Q0 ourem allele were identified among 43 patients with abnormally low serum AAT levels based on their genotypes for PI*S and PI*Z alleles. Since 4 out of 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.