Background: Alpha 1 antitrypsin (AAT) is a highly polymorphic protein, having more than 75 different variants. In this work two rare AAT deficient variants were characterized by DNA study.
Patients and methods: Members of three generations of two separate families were studied. In family 1, the index case was affected with pulmonary emphysema and presented AAT deficiency (23 mg/dl). In family 2, the index case had a normal pulmonary function, an AAT serum level of 72 mg/dl and a phenotype heterozygous for an AAT variant migrating in the P variant region. The AAT variants were characterized by polymerase chain reaction amplification of the coding exons and direct sequencing of the amplification products.
Results: Direct DNA sequencing from a member of family 1 demonstrates that in the exon II of the normal M1 (Val213) allele there was a 3-bp deletion (TTC), corresponding to Phe51 or Phe52. This mutation is characteristic of the Pl Mpalermo variant. In our study, Pl Mpalermo was detected in six members of three generations of this same family. Sequencing of exon III in a member of family 2, identified in the common M1 (Val213) allele a single base substitution of GAT-GTT, with the resulting amino acid change Asp256 for Val256. This mutation characterizes the Pl Plovel allele. The Pl Plovel was also detected in nine members of five others independent families. All of them have AAT serum levels between 80 and 102 mg/dl. None of the studied subjects had clinical evidence of lung disease.
Conclusions: The results of our study show the presence of the two AAT deficient variants in Spain and suggest that the Pl Plovel variant might be more common than expected.