Table 3.
AIP Pathogenic or Likely Pathogenic Mutations in the Familial and Sporadic Cohorts
| Mutation (DNA Level [Protein Level]) | Mutation Type | Pathogenic | Location in Protein | Familial Cohort (n = 238)a | Simplex Cohort (n = 52)a | Combined (n = 290)a | References/SRb |
|---|---|---|---|---|---|---|---|
| g.4856_4857CG>AA | Promoter | Yesc | Not in protein (5′ UTR) | 3 (1.3) | — | 3 (1) | (3, 12)/(SR30) |
| c.3G>A (p.?) | Start codon | Likelyc | N terminus | 2 (0.8) | — | 2 (0.7) | This paper |
| c.40C>T (p.Q14*) | Nonsense | Yesc | N terminus | 2 (0.8) | — | 2 (0.7) | (1)/(SR31, 32) |
| c.70G>T (p.E24*) | Nonsense | Yesc | N terminus | 9 (3.8) | — | 9 (3.1) | (3)/(SR33) |
| c.74_81delins7 (p.L25Pfs*130) | Frameshift | Yesc | PPIase domain | 10 (4.2) | — | 10 (3.4) | (12)/(SR34) |
| c.100–1025_279 + 357del (ex2del) (p.A34_K93del) | Large genomic deletion | Yesc | PPIase domain | 12 (5) | 2 (4) | 14 (4.8) | (SR35) |
| c.100–18C>T | Intronic | Likely | Not in protein (intron 1) | — | 3 (6) | 3 (1) | (3, 7, 10)/(SR31) |
| c.241C>T (p.R81*) | Nonsense | Yesc | PPIase domain | 12 (5) | 4 (8) | 16 (5.5) | (3)/(SR30, 36–38) |
| c.249G>T (p.G83Afs*15) | Splice site (cryptic splice site) | Yesc | PPIase domain | 4 (1.7) | — | 4 (1.4) | (12) |
| c.338_341dup (p.L115Pfs*16) | Frameshift | Yesc | PPIase domain | — | 2 (4) | 2 (0.7) | (6) |
| c.427C>T (p.Q143*) | Nonsense | Yesc | Between PPIase and TPR1 domains | — | 1 (2) | 1 (0.3) | This paper |
| c.469–2A>G (p.E158_Q184del) | Splice site | Likely | TPR1 domain | — | 1 (2) | 1 (0.3) | (5)/(SR39, 40) |
| c.490C>T (p.Q164*) | Nonsense | Yesc | Between PPIase and TPR1 domains | 3 (1.3) | — | 3 (1) | (12) |
| c.570C>G (p.Y190*) | Nonsense | Yesc | TPR1 domain | 9 (3.8) | — | 9 (3.1) | This paper |
| c.662dupC (p.E222*) | Nonsense | Yesc | Between TPR1 and 2 domains | 3 (1.3) | — | 3 (1) | (12) |
| c.713G>A (p.C238Y) | Missense | Yes | TPR2 domain | 4 (1.7) | — | 4 (1.4) | (3)/(SR33) |
| c.783C>G (p.Y261*) | Nonsense | Yesc | TPR2 domain | 4 (1.7) | — | 4 (1.4) | (9)/(SR39, 41, 42) |
| c.787 + 9C>T | Intronic | Uncertain | Not in protein (intron 5) | — | 1 (2) | 1 (0.3) | This paper |
| c.804C>A (p.Y268*) | Nonsense | Yesc | TPR3 domain | 19 (8) | 3 (6) | 22 (7.6) | (SR43, 44) |
| c.805_825dup (p.F269_H275dup) | In-frame insertion | Yes | TPR3 domain | 16 (6.7) | 2 (4) | 18 (6.2) | (3)/(SR30, 39, 45) |
| c.807C>T (p.(=)) | Splice site (reduced transcript level) | Yes | TPR3 domain | 7 (2.9) | 4 (8) | 11 (3.8) | (3, 5, 7, 10, 12)/(SR46, 47) |
| c.811C>T (p.R271W) | Missense | Yes | TPR3 domain | — | 1 (2) | 1 (0.3) | (2, 7, 12)/(SR48) |
| c.816delC (p.K273Rfs*30) | Frameshift | Yesc | TPR3 domain | — | 1 (2) | 1 (0.3) | This paper |
| c.868A>T (p.K290*) | Nonsense | Yesc | TPR3 domain | — | 1 (2) | 1 (0.3) | This paper |
| c.872_877delTGCTGG (p.V291_L292del) | In-frame deletion | Yes | TPR3 domain | — | 1 (2) | 1 (0.3) | This paper |
| c.910C>T (p.R304*) | Nonsense | Yesc | C-terminal α-helix | 88 (37) | 16 (31) | 104 (35.9) | (1–3, 5, 7, 9, 12, 14)/ (SR39, 49–51) |
| c.911G>A (p.R304Q) | Missense | Yes | C-terminal α-helix | 20 (8.4) | 3 (6) | 23 (7.9) | (3, 5, 7, 9, 12)/(SR31, 39, 52, 53) |
| c.967delC (p.R323Gfs*39) | Frameshift | Yesc | C-terminal α-helix | — | 4 (8) | 4 (1.4) | This paper |
| c.976_977insC (p.G326Afs*?) | Frameshift | Yesc | C-terminal α-helix | — | 1 (2) | 1 (0.3) | This paper |
| c.978dupG (p.I327Dfs*?) | Frameshift | Yesc | C-terminal α-helix | — | 1 (2) | 1 (0.3) | This paper |
| c.1-?_993+?del− (whole gene deletion) | Large genomic deletion | Yesc | Absence of the whole protein | 11 (4.6) | — | 11 (3.8) | (12) |
Abbreviations: PPIase, peptidylprolyl isomerase; SR, supplemental references; TPR, tetratricopeptide repeat; UTR, untranslated region.
Dash indicates no individuals in this category.
a
Number of positive individuals for each mutation, considering the AIPmut-positive tested individuals, the obligate carriers, and the predicted AIPmut patients.
b
For supplemental references, see Supplemental Material.
c
Truncating mutation.