Mutations identified in compound heterozygotes with missense mutations in both alleles of PRF1
PFP genotype ID (age at HLH diagnosis, mo) and amino acid substitution . | Amino acid . | . | Predicted domain . | Lytic activity, % of WT PFP . | |
|---|---|---|---|---|---|
| . | Rodent . | Flounder . | . | . | |
| S15 (120) | |||||
| Pro39His | Pro | Pro | N-terminal | 0 | |
| Gly149Ser | Gly | Gly | ? | 0 | |
| T9 (24) | |||||
| Gly149Ser | Gly | Gly | ? | 0 | |
| Arg299Cys | Arg | Arg | ? | 0 | |
| U9 (48) | |||||
| Gly149Ser | Gly | Gly | ? | 0 | |
| Arg361Trp | Arg | Arg | ? | 0 | |
| V7 (NR) | |||||
| Val183Gly | Ala | Ser | ? | 100 | |
| Cys279Tyr* | Cys | Cys | ? | 0 | |
| W14 (6) | |||||
| Thr221Ile | Thr | Thr | α-helix | 0 | |
| Arg225Trp† | Thr | Thr | α-helix | 025 | |
| X7 (14, 17, 28) | |||||
| Arg225Trp† | Thr | Thr | α-helix | 025 | |
| Gly429Glu† | Gly | Gly | C2 | 3025 | |
PFP genotype ID (age at HLH diagnosis, mo) and amino acid substitution . | Amino acid . | . | Predicted domain . | Lytic activity, % of WT PFP . | |
|---|---|---|---|---|---|
| . | Rodent . | Flounder . | . | . | |
| S15 (120) | |||||
| Pro39His | Pro | Pro | N-terminal | 0 | |
| Gly149Ser | Gly | Gly | ? | 0 | |
| T9 (24) | |||||
| Gly149Ser | Gly | Gly | ? | 0 | |
| Arg299Cys | Arg | Arg | ? | 0 | |
| U9 (48) | |||||
| Gly149Ser | Gly | Gly | ? | 0 | |
| Arg361Trp | Arg | Arg | ? | 0 | |
| V7 (NR) | |||||
| Val183Gly | Ala | Ser | ? | 100 | |
| Cys279Tyr* | Cys | Cys | ? | 0 | |
| W14 (6) | |||||
| Thr221Ile | Thr | Thr | α-helix | 0 | |
| Arg225Trp† | Thr | Thr | α-helix | 025 | |
| X7 (14, 17, 28) | |||||
| Arg225Trp† | Thr | Thr | α-helix | 025 | |
| Gly429Glu† | Gly | Gly | C2 | 3025 | |
The original reference for each patient PFP genotype is shown in the first column as a superscript. Amino acid conservation is derived from the amino acid sequence alignment of mammalian and flounder perforins, as in PredictProtein28 (EMBL-Heidelberg). PFP indicates perforin; ?, unknown domain; and NR, not reported.
Shown in Figure 5.
Perforin mutations analyzed previously by us elsewhere.25,26