Table 1 Molecular and clinical features of known 21 PI*QO (Null) alleles
Allele | Molecular basis of disease | Clinical features | Reference |
|---|---|---|---|
QOamersfoort | Exon 2. Tyr160 stop. Nonsense mutation producing a stop at codon 160, and a premature termination in exon 2 with no detectable mRNA | The index patient was a Caucasian 47-year-old female patient who had COPD | [30] |
QObellingham | Exon 3. Lys217 stop codon. | High risk of emphysema in homozygotes and compound heterozygotes | [31] |
No detectable AAT mRNA | |||
QObolton | Exon 5. Δ1bpPro362 causing stop codon at 373. Truncated protein, degraded, not secreted | High risk of emphysema in homozygotes and compound heterozygotes | [17] |
QObonny blue | ΔG deletion position #1 of intron II splice acceptor | High risk of emphysema in homozygotes and compound heterozygotes | [4] |
QOcairo | Exon 3. Lys259 stop codon. Truncated protein, degraded, not secreted protein. | High risk of emphysema in homozygotes. One carrier belonged to an Italian/Egyptian family, and 2 other to a family from Southern Italy | [26] |
QOclayton | Exon 5. Pro362 insC causing stop codon at 376. Truncated protein, degraded and not secreted | High risk of emphysema in homozygotes and compound heterozygotes | [14] |
QOdevon (=QOnewport) | Exon 2. Gly115Ser. Intracellular degradation and reduced serum concentration | Risk of emphysema and liver disease in compound heterozygotes with Z allele. Unclear whether Gly115Ser would cause disease in absence of Z mutation | [32] |
QOgranite falls | Exon 2. Δ1bpTyr160 causing stop codon. No detectable AAT mRNA | Severe emphysema reported in an American black family Z compound heterozygote | [21] |
QOhong Kong | Exon 4. Δ2bpLeu318 causing stop codon at 334. Truncated protein; degraded and not secreted | High risk of emphysema in homozygotes and compound heterozygotes. Reported in Chinese descents. | [24] |
QOisola di procida | Δ17 Kb inc. exons II –V. No detectable AAT mRNA | Emphysema reported in compound heterozygote | [33] |
QOlisbon | Exon 2. Thr68Ile. | High risk of emphysema in homozygotes. | [16] |
50% normal serum AAT in M/QOLisbon heterozygotes | |||
QOludwisghafen | Exon 2. Ile92Asn. Intracellular degradation and no secreted protein | High risk of emphysema in homozygotes and compound heterozygotes | [18] |
QOmadrid | Intron 1C, c.-5 + 2dupT. Duplication of thymine in position +2 of the donor splice site, causing no expression of mRNA transcripts | Index case: a compound heterozygote QOmadrid /QOporto with COPD. Three heterozygote siblings with radiological findings of lung disease. | [current report] |
QOmattawa (M1allele) and QOourém (M3 allele) | Exon 5. Same mutation Leu353Phe causing stop codon at 376, in M1 and M3 respectively. Truncated protein, degraded, not secreted, reduced serum levels | Lung emphysema reported in homozygotes | |
QOmilano | Exon 3, 17 bp deletion (AAA CTA CAG CAC CTG GA), causing a stop codon downstream. Truncated protein lacking of active site | Heterozygote M/QOmilano Italian child with persistently increased in liver enzymes and a mild decrease in serum AAT levels | [23] |
QOnew hope | Exon 4, 5. Gly 320 GGG → Glu GAG/Glu 342 GAG → Lys AAG | High risk of emphysema in homozygotes and compound heterozygotes | [4] |
QOporto | Intron 1C, c.-5 + 1G > A. Splicing site variant, causing no expression of mRNA transcripts. | High risk of emphysema in homozygotes. | [29] |
QOriedenburg | Whole gene deletion. No AAT gene expression | High risk of emphysema in homozygotes and compound heterozygotes | [22] |
QOsaarbueken | Exon 5. 1158dupC causing stop codon at 376. Truncated protein; not secreted | High risk of emphysema in homozygotes. | [16] |
50% normal serum AAT in M/QO Saarbueken heterozygotes | |||
QOsoest | Exon 2. Thr102delA, which produces a TGA stop signal at codon 112 | Index case: a homozygote 46-year-old man with severe COPD | [30] |
QOtrastevere | Exon 3. Try194 stop codon. Intracellular degradation of truncated protein; not secreted | Emphysema reported in an Italian compound heterozygote | [20] |
QOwest | G → T position +1 of intron 2 splice donor substitution. ΔGly164- Lys191. Aberrant mRNA splicing, intracellular degradation and no detectable protein | Emphysema reported in a compound heterozygote | [34] |