Table V.
Clinical Data Collection of 89 FHL2 Patients Harboring Perforin Mutations Reported in the Literature
| Mutationa | Patient/case ID as in the reference | Nucleotide sequence alteration | Country of origin | Consanguinity/family history | Age at diagnosis (d: day, m: month, y: year)/sex | CNS | F | S | C | H/H | H | Treatment | BMT status/outcome/survival after diagnosis | Reference (PMID) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Trp374Stop | 1 | 1122 G→A | Turkey | +/+ | 2 m/M | − | + | + | + | + | + | Vp/Cs/CsA | No BMT/dead | 11179007 |
| 7 | 1122 G→A | Turkey | −/+ | 1 m/F | + | + | + | + | Vp/Cs | No BMT/dead | 11179007 | |||
| 11 | 1122 G→A | Turkey | +/+ | 39 m/M | + | + | + | + | + | HLH–94 | BMT/alive and well | 11179007 | ||
| 17 | 1122 G→A | Turkey | +/+ | 10 m/F | + | + | + | + | + | No treatment | No BMT/dead | 11179007 | ||
| Case 1 | Turkey | 1st/− | 7 d/M | − | No treatment | 2 d | 18190960 | |||||||
| Case 2 | Turkey | 2nd/+ | 4 m/M | − | Steroid | 7 d | 18190960 | |||||||
| Case 3 | Turkey | 1st/+ | 6 m/F | + | HLH–94 | 1 m | 18190960 | |||||||
| Patient 21 | 1122 G→A | Turkey | +/+ | 12060139 | ||||||||||
| Patient 34 | 1122 G→A | Turkey | +/+ | 12060139 | ||||||||||
| Patient 62 | 1123 G→A | Turkey | +/+ | 12060139 | ||||||||||
| Case 7 | 1123 G→A | Turkey | +/+ | 3 m/M | − | + | + | + | BMT/alive | 11565555 | ||||
| Case 8 | 1123 G→A | Turkey | +/+ | 2.5 m/F | + | + | + | + | BMT/alive | 11565555 | ||||
| Case 10 | 1123 G→A | Turkey | +/− | 2 m/M | − | + | + | + | BMT/alive | 11565555 | ||||
| Ile224Asp | 3 | 671 T→A | Sweden | +/− | 58 m/F | + | + | + | + | + | Vp/Cs/CsA | BMT/alive, mild retardation | 11179007 | |
| Tyr219Stop/Val50Met | 9 | 657 C→A/148 G→A | Turkey | −/− | 4 m/M | + | + | + | + | + | HLH–94 | No BMT/dead | 11179007 | |
| Lys285Del | 33 | 853–855 del AAG | Turkey | −/− | 3 m/F | + | + | + | + | + | No treatment | No BMT/dead | 11179007 | |
| Gly149Ser | Case 4 | Turkey | 2nd/+ | 26 d/M | + | HLH–94 | 10 m | 18190960 | ||||||
| Case 5 | Turkey | 3rd/+ | 14 m/F | + | HLH–2004 | 8 m | 18190960 | |||||||
| Val50Met | Case 6 | Turkey | 1st/− | 16 y/M | + | HLH–2004 | Alive | 18190960 | ||||||
| Ala91Val | Case 7 | Turkey | 1st/− | 13 y/F | + | HLH–2004 | Alive | 18190960 | ||||||
| Case 8 | Turkey | 3rd/+ | 12 y/M | − | HLH–2004 | 1.5 y | 18190960 | |||||||
| II-2 | 272 C→T | Spain | −/ | 49 y/M | − | + | + | 16956828 | ||||||
| Ala523Asp | Case 9 | Turkey | 1st/+ | 36 m/F | + | HLH–2004 | 2 m | 18190960 | ||||||
| Pro89Thr | Family 1-Case A | 265 C→A | Oman | +/+ | 1 m/F | − | + | + | + | + | HLH–94 | BMT/alive | 14578030 | |
| Family 7-Case A | 265 C→A | Oman | +/− | 2 m/F | − | + | + | + | + | HLH–94 | BMT/alive | 14578030 | ||
| Gly45Arg/Arg54Ser | P10 | 133 G→A/160 C→T | Hispanic | 3 y/F | 11756153, 14757862 | |||||||||
| Pro39His/Gly149Ser | P1 | 116 C→A/445 G→A | White | 10 y/F | 11756153, 14757862 | |||||||||
| Ser150Stop/Arg225Trp | P12 | 449 C→A/673 C→T | White | 5 y/F | 11756153, 14757862 | |||||||||
| Leu17Stop | P9 | 50delT | African/American | 3 m/F | 11756153, 14757862 | |||||||||
| P11 | 50delT | African/American | 8 m/M | 11756153, 14757862 | ||||||||||
| Patient 4 | 50delT | Algeria | +/+ | 12060139 | ||||||||||
| Patient 92 | 50delT | Haiti | +/+ | 12060139 | ||||||||||
| P21 | 50delT | African/American | 2 m/M | 14757862 | ||||||||||
| P30 | 50delT | African/American | 2 m/M | 14757862 | ||||||||||
| P59 | 50delT | African/American | 3 m/M | 14757862 | ||||||||||
| P26 | 50delT | African/American | 6 m/F | 14757862 | ||||||||||
| P31 | 50delT | African/American | 6 m/F | 14757862 | ||||||||||
| P56 | 50delT | African/American | 14757862 | |||||||||||
| Case 1 | 50delT | Ghana | +/− | 2 m/M | − | + | + | + | BMT/alive | 11565555 | ||||
| Val38Leu/??? | Middle East | 18710388 | ||||||||||||
| Glu46Stop/Ala91Val+Arg119Trp | 4-year-old girl | Russia (German descent) | −/− | 4 y/F | HLH–94 | BMT/alive | 17328077 | |||||||
| Tyr450Met | Case 1 | 1349 C→T | Japan | 7 y/F | + | + | + | + | + | + | HLH–94,CHOP | BMT/alive | 12716377, 15632205, 17266056 | |
| Met1Val/Gly317Arg | Case 2 | 1 A→G/949 G→A | Japan | /+ | 11 y/F | + | + | + | + | + | - | HLH–94 | No BMT/alive | 12716377, 15632205, 17266056 |
| Arg410Trp/Leu364fs | Case 3 | 1228 C→T/1090.91delCT | Japan | 12/F | − | + | + | + | + | + | PSL, CsA | 12716377, 15632205, 17266056 | ||
| Met1I/Asp62fsX12 | Patient 2 | 3 G→A/185_195del11 | Germany | −/ | 2 m/ | 16278825 | ||||||||
| Val38Met/Ala91Val | Patient 19 | 112 G→A/272 C→T | Morocco | +/ | 6 m/ | 16278825 | ||||||||
| Gly149Ser/Ala262fsX22 | Patient 3 | 445 G→A/786_801del16 | Germany | −/ | 2 m/ | 16278825 | ||||||||
| Gly149Ser | Patient 16 | 445 G→A | Turkey | +/ | 3 m/ | 16278825 | ||||||||
| P50 | 445 G→A | Hispanic | 6 m/M | 14757862 | ||||||||||
| Pro201Thr/Lys285Del | Patient 17 | 601 C→A/853_855delAAG | Turkey | −/ | 10 y/ | 16278825 | ||||||||
| His222Gln/Arg232His | Patient 18 | 666 C→A/695 G→A | Italy | −/ | >10 y/ | 16278825 | ||||||||
| Arg240Gly | Patient 20 | 718 C→G | Greece | +/ | 12 m/ | 16278825 | ||||||||
| Leu526fsX87 | Patient 1 | 1576delT | Germany | +/ | 10 m/ | 16278825 | ||||||||
| Arg225Trp/Gly429Glu | Patient 5 | 673 C→T/1286 G→A | Africa | −/+ | 12060139 | |||||||||
| Pro345Leu | Patient 6 | 1034 C→T | Africa | +/+ | 12060139 | |||||||||
| Cys279Tyr/Val183Gly | Patient 11 | 836 G→A/548 T→G | France | −/− | 12060139 | |||||||||
| Asn252Ser/? | Patient 25 | 755 A→G/? | Italy | −/+ | 12060139 | |||||||||
| Arg232His/? | Patient 27 | 695 G→A/? | Italy | −/+ | 12060139 | |||||||||
| Gln64Stop | Patient 29 | 190 C→T | Algeria | +/− | 12060139 | |||||||||
| Met1Ile | Patient 30 | 3 G→A | Lebanon | +/+ | 12060139 | |||||||||
| Gln261Lys | Patient 82 | 781 G→A | Algeria | +/− | 12060139 | |||||||||
| Gly220Ser/Leu17Stop | Patient 95 | 658 G→A/50delT | Algeria | −/− | 12060139 | |||||||||
| Trp94Arg | Case 2 | 283 T→C | Italy | +/− | 3 m/M | − | + | + | + | BMT/alive | 11565555 | |||
| Tyr219Stop | Case 3 | 657 C→A | Italy | +/+ | 1.5 m/M | − | + | + | + | BMT/alive | 11565555 | |||
| Gly220Ser | Case 4 | 658 G→A | Italy | +/− | 1.5 m/F | + | + | + | + | Dead | 11565555 | |||
| Thr221Ile/Arg225Trp | Case 5 | 662 C→T/673 C→T | Italy | −/− | 6 m/F | + | + | + | + | Dead | 11565555 | |||
| Arg232Cys/Gly394Fs | Case 6 | 694 C→T/1182insT | Italy | −/− | 6 y/M | − | + | + | + | Dead | 11565555 | |||
| Phe193Leu/Arg410Pro | 577 T→C/1229 G→C | Caucasian | /− | 7 y/M | − | + | + | + | + | + | 14576041 | |||
| Val50Met | P35 | 148 G→A | Russia | 7 y/M | 14757862 | |||||||||
| Met1Ile/Asp70Tyr | P58 | 3 G→A/208 G→T | White | 8 y/M | 14757862 | |||||||||
| His222Arg/ | P22 | 665 A→G | White/Asian | 1 m/M | 14757862 | |||||||||
| Phe157Val/fs | P23 | 469 T→G/1628insT | White | 2 m/F | 14757862 | |||||||||
| Leu17Stop/Gln481Pro | P33 | 50delT/1442 A→C | Hispanic | 2 m/F | 14757862 | |||||||||
| Leu17Stop/Cys73Arg | P32 | 50delT/217 T→C | African/American | 4 m/M | 14757862 | |||||||||
| Leu17Stop/Gly45Glu | P34 | 50delT/134 G→A | African/American | 8 m/F | 14757862 | |||||||||
| His222Gln/fs | P28 | 666 C→A/1636delC | White | 3 m/M | 14757862 | |||||||||
| Arg225Trp | P57 | 673 C→T | Filipino | 2 y/M | 14757862 | |||||||||
| Gly149Ser/Arg299Cys | P25 | 445 G→A/895 C→T | Portugal | 2 y/M | 14757862 | |||||||||
| Gly149Ser/Arg361Trp | P24 | 445 G→A/1081 A→T | Hispanic | 4 y/F | 14757862 | |||||||||
| Arg225Trp | P29 | 673 C→T | White | 5 y/F | 14757862 | |||||||||
| Met1Ile/Asp313Val | P27 | 3 G→A/938 A→T | White | 14757862 | ||||||||||
| Ala91Val-Arg231His/Ala91Val | Proband (twin) | 272 C→T-695 G→A/272 C→T | ? | /− | 13/F | − | + | + | + | + | + | 14739222 | ||
| Ala91Val/Trp374Stop | Sibling 1 | 272 C→T/1122 G→A | Italy | 27 y/M | + | + | + | + | + | No BMT/alive | 12229880 | |||
| Sibling 2 | 272 C→T/1122 G→A | Italy | 25.5/F | + | + | + | + | + | BMT/alive | 12229880 | ||||
| Pro459Leu | Patient 1 | 1376 C→T | Algeria | +/− | 9 m/M | + | − | + | − | Dead | 15598808 | |||
| Patient 2 | 1376 C→T | Algeria | +/− | 33 m/M | + | + | + | + | + | Dead | 15598808 | |||
| Thr435Met | Patient W. | 1304 C→T | 12599189 | |||||||||||
| His222Gln | Patient 1 | 666 C→A | Netherlands | +/ | 2 m/F | + | + | + | + | + | SCT/alive and well | 17525286 | ||
| Glu317Arg/Asp430Tyr | Patient 2 | 949 G→A/1288 G→T | Sweden | 0 m/M | + | + | + | + | + | Dead | 17525286 |
a
If single mutation is shown, it is homozygous; otherwise mutations are compound heterozygous.
+, finding is present; −, finding is not present; M, male; F, female; fs, frameshift; ins, insertion; BMT, bone marrow transplantation; SCT, stem cell transplantationSymptoms: CNS, central nervous system involvement; F, fever; S, splenomegaly; C, cytopenia; H/H, hypertriglyceridemia and/or hypofibrinogenemia; H, hemophagocytosis.