MOLECULAR CHARACTERIZATION OF THE 2 DEFICIENT VARIANTS OF ALPHA-1-ANTITRYPSIN - PI MPALERMO AND PI PLOVEL

BACKGROUND: Alpha 1 antitrypsin (AAT) is a highly polymorphic protein, having more than 75 different variants. In this work two rare AAT def icient variants were characterized by DNA study. PATIENTS AND METHODS: Members of three generations of two separate families were studied. I n family 1, the index case was affected with pulmonary emphysema and p resented 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 phenot ype heterozygous for an AAT variant migrating in the P variant region. The AAT variants were characterized by polymerase chain reaction ampl ification of the coding exons and direct sequencing of the amplificati on products. RESULTS: Direct DNA sequencing from a member of family 1 demonstrates that in the exon II of the normal M1 (Val(213)) allele th ere was a 3-bp deletion (TTC), corresponding to Phe(51) or Phe(52), Th is mutation is characteristic of the PI Mpalermo variant. In our study , PI Mpalermo was detected in six members of three generations of this same family, Sequencing of exon III in a member of family 2, identifi ed in the common M1 (Val(213)) allele a single base substitution of GA T-GTT, with the resulting amino acid change Asp(256) for Val(256). Thi s mutation characterizes the PI Plovel allele. The PI Plovel was also detected in nine members of five others independent families. All of t hem have AAT serum levels between 80 and 102 mg/dl. None of the studie d subjects had clinical evidence of lung disease, CONCLUSIONS: The res ults of our study show the presence of the two AAT deficient variants in Spain and suggest that the PI Plovel variant might be more common t han expected.