Table 1.
Overview of patient characteristics and rare/novel sequence variants identified by next-generation sequencing
| Patient ID | AAT serum level (mg/dL) | CRP (mg/dL) | Previous phenotypes | Age (yrs) | Sex | NGS DNA analysis | ||
|---|---|---|---|---|---|---|---|---|
| Novel mutant nucleotide changes | Consequence | Genotype | ||||||
| Splice variants | ||||||||
| 2250 | 70 | 5.9 | – | 65 | F | Novel splice variant: G > C at position +1 of intron 1C | E376D – M3 allele | |
| 24023 | 62.8 | – | 71 | M | 917 + 1G > A | Affects the normal mRNA splicing. | E376D – M3 allele | |
| Deletions | ||||||||
| 10724 | 52 | 7.3 | M3 | 49 | M | A347fs: Novel 1 bp deletion (1112delC) at position 347 | Frameshift that extends the protein by 5 amino acids | E376D – M3 allele |
| Stop codons | ||||||||
| 6326e | 2 | 0 | Z/M1 | 57 | F | Q156X: C > T at Chr14:94849037 (GRCh.37.p13) c.538C > T | Insertion of stop codon at position 156 | Q156X E342K – Z allele V213A – M1 allele |
| 6376e | 98 | 7 | I | 54 | M | Q156X: C > T at Chr14:94849037 (GRCh.37.p13) c.538C > T | Insertion of stop codon at position 156 | Q156X R39C – I allele |
| 19771 | 91.4 | – | M | 57 | G192Fs: 1 bp deletion at Chr14:94847477 (GRCh37.p13) c.647_647delG | Predicted to produce a premature stop codon at amino acid 214, leading to a premature termination on exon III | ||
| Single-nucleotide variations | ||||||||
| CA97 | 112 | – | M3 M2/4 | 65 | F | GAG > AAG |
E204K – rarea E376D – M3 allele R101H – M2/M4 allele |
|
| 1144 | 72 | – | M1 | 61 | M | CCC > TCC | P289S – rarea V213A – M1 allele | |
| 2343 | 86 | 3.6 | M1 | 60 | F | ATC > AAC | I9N [includes precursor] – rarea V213A – M1 allele | |
| 4293d | 66 | 0.5 | M1 | 54 | M | CCC > CTC | Q0Bellingham – insertion of stop codon at position 156 | P28L – rarea K217X – Q0Bellingham V213A – M1 allele |
| 5564d | 67 | 1.6 | M1 | 51 | F | CCC > CTC | Q0Bellingham – insertion of stop codon at position 156 | P28L – rarea K217X – Q0Bellingham V213A – M1 allele |
| 4668 | 78 | 2.2 | M3 | 62 | M | ATC > AAC | I50N (PiTijarafe) – rare E376D – M3 allele | |
| 9533 | 73 | 0.9 | – | 60 | M | ATG > ACG | M385 T – rarec M allele | |
| 10889 | – | 12.5 | M3 | 34 | F | CAG > CGG | Q40R – rarea E376D – M3 allele | |
| 12642 | 89 | 0.6 | M3 | 66 | F | GAC > CTC | D341V – rareb E376D – M3 allele P = L118 – no amino acid change | |
| 14271 | 47 | 0.6 | Z/M1 | 61 | F | ATG > ACG | M221 T – rarea V213A – M1 allele E342K – Z allele | |
| 15230 | 34 | 1 | Z/M1 | 72 | M | GTG > GAG | V210E (Ncambodia/Pierre-bénite) – rarea V213A – M1 allele E342K – Z allele | |
| 17,657 | 160 | 1.5 | M3/M4 | 87 | M | AAG > GAG | K174E – NOVELa E376D – M3 allele R101H – M2/M4 allele | |
| 21034 | 121.2 | – | – | 47 | F | CCC > CAC |
P369H – rare E264V – S allele |
|
| 21636 | 88.4 | – | – | 58 | M | GTG > ATG | V333 M – rarec E376D – M3 allele R101H – M4 allele | |
| 23523 | 118.6 | – | – | 48 | F | GCA > CCA | A325P (Nvestenanova) – rarea R223C – F allele E376D – M3 allele R101H – M4 allele | |
| 24319 | 79.3 | – | – | 57 | F | GCC > GAC |
A142D – rarec E264V – S allele V213A – M1 allele |
|
| 76430 | 74.8 | – | – | 59 | M | CAC > TAC | H262Y – rarec M allele | |
All SNVs are reported without the 24 amino acid precursor unless otherwise stated
aSNVs have been previously reported in dbSNP (E204K – rs199422208; P289S – rs779938258; Q40R – rs763483402; M221 T – rs766260108; K174E – rs766034720; I9N [includes precursor] – rs1296175763; P28L – rs944607375)
bSNVs have been previously reported in dbSNP and linked to AATD (D314V – rs864622046)
cSNV previously reported in the literature (20–26) (H262Y – rs149537225; V333 M – 373,630,097; A142D – rs142942004; V210E – rs746197812; M385 T – rs1488213352; A325P – rs376024688; I50N – rs1275309068)
dFamilial samples from brother (4293) and sister (5564)
eFamilial samples from brother (6376) and sister (6326)
bp Base pair, dbSNP Database of single nucleotide polymorphisms, SNV Single nucleotide variation