Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency

The Italian Registry for Severe AATD was established in 1996 as a result of a nationwide screening programme sponsored by the two major Italian scientific respiratory societies.10 Although Italy is considered a country with a medium-low prevalence of AATD (mean PI*Z gene frequency: 0.0013),11 the programme succeeded in identifying a relatively large cohort of AATD individuals. During the development of the screening program, we noticed that, in addition to the groups of AATD individuals carrying the PI*ZZ and PI*SZ genotypes, there was an unexpectedly large group of subjects carrying at least one rare AATD allele. We therefore decided to study this group of subjects, focusing particularly on characterising their clinical phenotypes.