Table 1.
Two Individuals with Alpha-1 Antitrypsin Deficiency Incidentally Discovered through Genetic Sequencing
| Case 1 | Case 2 | |
|---|---|---|
| Age, yr | 45 | 32 |
| Sex | Male | Male |
| Alpha-1 antitrypsin genotype | PI*SZ | PI*Z-Null† |
| Alpha-1 antitrypsin level, μM | 9.2 | 4.8 |
| Alpha-1 antitrypsin level, mg/dl | 48 | 25 |
| FEV1, L (% predicted) | 4.68 (112) | 5.21 (104) |
| FVC, L (% predicted) | 6.08 (117) | 6.27 (100) |
| FEV1/FVC ratio | 0.77 | 0.83 |
| Total lung capacity, L (% predicted) | 7.49 (104) | 6.77 (82) |
| DlCO, ml/min/mm Hg (% predicted) | 29.6 (90) | 38.4 (97) |
†
Sequencing showed SERPINA1 heterozygosity, with one PI*Z allele and a complex frameshift mutation, g.94378591_94378598delGCAGCTTCinsTGTTTTT (NC_000014.9), between amino acid positions Glu346 and Ala348. This mutation leads to a premature stop codon at amino acid position 353, leading to a null allele, confirmed by isoelectric focusing of serum, which showed only Pi Z protein. This null allele had not been previously described and has been reported to the National Center for Biotechnology Information dbSNP database as rs864622043.