Table 1.
Adult primary HLH gene pathogenic variants
| patient number | age at diagnosis | gender | involved gene | site and type of pathogenic variants | change in amino acid | NM_ | Polyphen2(HDIV) | SIFT | ExAC_ALL | HGMD (Disease) |
|---|---|---|---|---|---|---|---|---|---|---|
| P01 | 18 | F | PRF1 | c.1168C > T (heterozygous nonsense pathogenic variant) | p. R390X |
NM_001083116 NM_005041 |
– | – | 0.000008654 | Cytophagic histiocytic panniculitis |
| c.1349C > T (heterozygous missense pathogenic variant) |
p.T450 M | 1 | 0.001 | 0.00004957 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P02 | 19 | M | PRF1 | c.1349C > T (homozygous missense pathogenic variant) | p.T450 M |
NM_001083116 NM_005041 |
1 | 0.001 | 0.00004957 | Haemophagocytic lymphohistiocytosis, familial |
| P03 | 18 | M | PRF1 | c.172 T > C (heterozygous missense pathogenic variant) | p. S58P |
NM_001083116 NM_005041 |
0.159 | 0.055 | – | – |
| c.1083_1094del(heterozygou s non-frameshift pathogenic variant) | p.361_365del | – | – | – | – | |||||
| P04 | 54 | F | PRF1 | c.65delC (heterozygous frameshift pathogenic variant) | p. P22RfsX29 |
NM_001083116 NM_005041 |
– | – | 0.0000108 | Haemophagocytic lymphohistiocytosis, familial |
| c.674G > A (heterozygous missense pathogenic variant) | p.R225Q | 0.05 | 0.366 | 0.0001 | – | |||||
| P05 | 27 | M | PRF1 | c.503G > A (heterozygous missense pathogenic variant) | p. S168 N |
NM_001083116 NM_005041 |
0.035 | 0.45 | 0.00002473 | Haemophagocytic lymphohistiocytosis, familial |
| c.65delC (heterozygous missense pathogenic variant) |
p.P22RfsX29 | – | – | 0.0000108 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P06 | 18 | F | PRF1 | c.1090_109ldel(heterozygous frameshift pathogenic variant) | p. T364fsX93 |
NM_001083116 NM_005041 |
– | – | 0.000008701 | Haemophagocytic lymphohistiocytosis, familial |
| c.1349C > T (heterozygous missense pathogenic variant) |
p.T450 M | 1 | 0.001 | 0.00004957 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P07 | 18 | M | PRF1 | c.65delC (heterozygous frameshift pathogenic variant) | p. P22RfsX29 |
NM_001083116 NM_005041 |
– | – | 0.0000108 | Haemophagocytic lymphohistiocytosis, familial |
| c.1349C > T (heterozygous missense pathogenic variant) |
p.T450 M | 1 | 0.001 | 0.00004957 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P08 | 18 | F | PRF1 | c.380A > G (heterozygous missense pathogenic variant) | p. N127S |
NM_001083116 NM_005041 |
0.999 | 0 | – | – |
| c.853_855delAAG(heterozygous frameshift pathogenic variant) | p.K285del | – | – | 0.00005766 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P09 | 18 | F | PRF1 | c.46C > T (heterozygous missense pathogenic variant) | p. P16S |
NM_001083116 NM_005041 |
0.995 | 0.19 | – | – |
| c.1066C > T (heterozygous missense pathogenic variant) |
p.R356W | 0.208 | 0.016 | 0.000008576 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P10 | 36 | M | PRF1 | c.133G > A (heterozygous missense pathogenic variant) | p. G45R |
NM_001083116 NM_005041 |
1 | 0 | – | Haemophagocytic lymphohistiocytosis, familial |
| c.1228C > T (heterozygous missense pathogenic variant) | p. R410W | 1 | 0.009 | 0.00005111 | Haemophagocytic lymphohistiocytosis, familial | |||||
| UNC1 3D |
c. 1280G > A (heterozygous missense pathogenic variant) | p.R427Q | NM_199242 | 1 | 0.005 | 0.00008298 | – | |||
| P11 | 52 | M | UNC13D | c.2588G > A (homozygous missense pathogenic variant) | p.G863D | NM_199242 | 1 | 0 | 0.0004 | Haemophagocytic lymphohistiocytosis, familial |
| P12 | 24 | F | UNC13D | c.407G > A (heterozygous missense pathogenic variant) | p.C136Y | NM_199242 | 1 | 0 | – | – |
| c.640C > T (heterozygous nonsense pathogenic variant) |
p.R214X | – | – | 0.00000824 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P13 | 28 | M | UNC13D | c.3134C > T (heterozygous missense pathogenic variant) | p. T1045 M | NM_199242 | 0.598 | 0.158 | 0 | – |
| c.2553 + 5C > G (heterozygous missense pathogenic variant) |
– | – | – | 0.0008 | Haemophagocytic lymphohistiocytosis, familial | |||||
| P14 | 18 | M | UNC13D | c.1120C > A(heterozygous missense pathogenic variant) | p.P374T | NM_199242 | 0.96 | 0.22 | – | – |
| LYST | c.11268-5 T > −(heterozygous missense pathogenic variant) | – | NM_000081 | – | – | – | – | |||
| P15 | 27 | M | PRF1 | c.127C > A (heterozygous missense pathogenic variant) | p. L43 M |
NM_001083116 NM_005041 |
0.926 | 0.099 | – | – |
| SH2D 1A |
c.7G > T(hemizygous missense pathogenic variant) | p.A3S |
NM_001114937 NM_002351 |
0 | 0.84 | 0.0002 | Lymphoproliferative syndrome, X-linked | |||
| P16 | 32 | M | SH2D1A | c.32 T > G (hemizygous missense pathogenic variant) | p.I11S |
NM_001114937 NM_002351 |
0.999 | 0.002 | – | – |
| P17 | 34 | F | RAB27a | c.244C > T (homozygous missense pathogenic variant) | p.R82C |
NM_004580 NM_183234 NM_183235 NM_183236 |
1 | 0 | 0.000008303 | Immunodeficiency |
| P18 | 32 | F | LYST | c.8368A > C (heterozygous missense pathogenic variant) | p. K2790Q |
NM_000081 NM_001301365 |
0.38 | 0.021 | 0.0008 | – |
| c.11268-4A > T (heterozygous missense pathogenic variant) |
– | – | – | – |