Table 2.
Detailed gene variants information in genetically defined CN
| No. | Gene | Location | Nucleotide change | Protein level | Inheritance | Novel mutation∗ | Clinical significance† | Reference (PMID‡) |
|---|---|---|---|---|---|---|---|---|
| 1 | ELANE | Exon1 | c.1A>G | p.M1V | De novo | No | Pathogenic | 24184683 |
| 2 | ELANE | Exon1 | c.1A>G | p.M1V | De novo | No | Pathogenic | 24184683 |
| 3 | ELANE | Exon1 | c.3G>A | p.M1I | De novo | No | Pathogenic | 24184683 |
| 4 | ELANE | Exon2 | c.140T>G | p.L47R | De novo | Yes | Pathogenic | NA§ |
| 5‖ | ELANE | Exon2 | c.158A>G | p.H53R | De novo | No | Pathogenic | NA§ |
| 6 | ELANE | Exon2 | c.164G>A | p.C55Y | NA§ | No | Pathogenic | 16986121 |
| 7 | ELANE | Exon2 | c.164G>A | p.C55Y | Paternal | No | Pathogenic | 16986121 |
| 8 | ELANE | Exon2 | c.212G>T | p.C71F | De novo | No | Pathogenic | 31839986 |
| 9 | ELANE | Exon3 | c.242G>C | p.R81P | De novo | No | Likely Pathogenic | 16986121 |
| 10¶ | ELANE | Exon3 | c.269_277del | p.R91Afs∗175 | De novo | Yes | NA§ | NA§ |
| ELANE | Exon3 | c.278A>G | p.E93G | De novo | Yes | Pathogenic | NA§ | |
| 11‖ | ELANE | Exon3 | c.308G>T | p.R103L | De novo | No | Likely Pathogenic | 17761833 |
| 12 | ELANE | Exon3 | c.362T>C | p.L121P | De novo | No | Likely Pathogenic | NA§ |
| 13 | ELANE | Exon4 | c.368T>A | p.L123H | NA | Yes | Pathogenic | NA§ |
| 14 | ELANE | Exon4 | c.377C>T | p.S126L | De novo | No | Pathogenic | 28492532, 11001877, 14962902, 16079102, 16737875, 18611981, 20582973, 22758217, 23463630, 16551967, 26567890 |
| 15 | ELANE | Exon4 | c.401_415del | p.Q134 _L138del | De novo | Yes | NA§ | NA§ |
| 16‖ | ELANE | Exon4 | c.416C>T | p.P139L | NA | No | Pathogenic | 11001877, 23463630, 21425445, 14962902, 30040071, 16079102, 31321910, 31248972 |
| 17 | ELANE | Exon4 | c.452G>A | p.C151Y | NA§ | No | Pathogenic | 24523240, 25427142, 11675333, 23463630 |
| 18 | ELANE | Exon4 | c.452G>C | p.C151S | De novo | No | Pathogenic | 23463630 |
| 19 | ELANE | Exon4 | c.588delC | p.V197Sfs∗15 | Paternal | No | NA§ | 25427142 |
| 20 | ELANE | Exon4 | c.588delC | p.V197Sfs∗15 | Paternal | No | NA§ | 25427142 |
| 21‖ | ELANE | Exon4 | c.597+4C>G | splicing | NA§ | Yes | NA§ | NA§ |
| 22 | ELANE | Exon5 | c.601del | p.D201Tfs∗11 | De novo | Yes | NA§ | NA§ |
| 23 | ELANE | Exon5 | c.607G>C | p.G203R | NA§ | No | Pathogenic | 23463630 |
| 24 | ELANE | Exon5 | c.608G>A | p.G203D | De novo | Yes | Pathogenic | NA§ |
| 25 | ELANE | Exon5 | c.608G>A | p.G203D | De novo | Yes | Pathogenic | NA§ |
| 26 | ELANE | Exon5 | c.622T>C | p.C208R | paternal | Yes | Pathogenic | NA§ |
| 27 | ELANE | Exon5 | c.640G>A | p.G214R | De novo | No | Pathogenic | 11001877, 15657182, 16079102, 28073911, 30386760, 3229910 |
| 28 | ELANE | Exon5 | c.640G>A | p.G214R | De novo | No | Pathogenic | 11001877, 15657182, 16079102, 28073911, 30386760, 3229910 |
| 29 | ELANE | Exon5 | c.640G>A | p.G214R | De novo | No | Pathogenic | 11001877, 15657182, 16079102, 28073911, 30386760, 3229910 |
| 30 | ELANE | Exon5 | c.640G>A | p.G214R | De novo | No | Pathogenic | 11001877, 15657182, 16079102, 28073911, 30386760, 3229910 |
| 31 | ELANE | Exon5 | c.641G>A | p.G214E | De novo | No | Likely Pathogenic | NA§ |
| 32 | ELANE | Exon5 | c.651delC | p.F218fs | De novo | Yes | NA | NA§ |
| 33 | ELANE | Exon5 | c.658delC | p.R220fs∗20 | De novo | No | Pathogenic | 26174650 |
| 34 | ELANE | Exon5 | c.661G>T | p.G221X | De novo | No | Uncertain Significance | 11001877 |
| 35 | ELANE | Exon5 | c.684C>G | p.Y228X | De novo | No | NA§ | 32054657 |
| 36 | ELANE | Exon5 | c.704T>G | p.V235G | De novo | Yes | Pathogenic | NA |
| 37 | HAX1 | Exon3 | c.430dupG | p.V144Gfs∗5 | Maternal | No | Pathogenic | 28492532, 17187068, 18337561, 20065084, 20220065, 22102707, 24482108 |
| HAX1 | Exon5 | c.557-1G>C | splicing | Paternal | No | Likely Pathogenic | 16199547, 17187068 | |
| 38 | HAX1 | Exon2 | c.216_217insC | p.I73Hfs∗6 | Maternal | No | Pathogenic | 17187068 |
| HAX1 | Exon3 | c.430dupG | p.V144Gfs∗5 | Paternal | No | Pathogenic | 28492532, 17187068, 18337561, 20065084, 20220065, 22102707, 24482108 | |
| 39 | HAX1 | Exon3 | c.430dupG | p.V144Gfs∗5 | Maternal | No | Pathogenic | 28492532, 17187068, 18337561, 20065084, 20220065, 22102707, 24482108 |
| HAX1 | Exon3 | c.430dupG | p.V144Gfs∗5 | Paternal | No | Pathogenic | 28492532, 17187068, 18337561, 20065084, 20220065, 22102707, 24482108 | |
| 40 | HAX1 | Exon3 | c.486_487dup | p.Q163Pfs∗52 | Maternal | Yes | NA§ | NA§ |
| HAX1 | Exon3 | c.430dupG | p.V144Gfs∗5 | Paternal | No | Pathogenic | 28492532, 17187068, 18337561, 20065084, 20220065, 22102707, 24482108 | |
| 41 | CXCR4 | Exon2 | c.1000C>T | p.R334X | NA | No | Pathogenic | 31313072, 12692554, 25662009, 31493092 |
| 42 | CXCR4 | Exon2 | c.1000C>T | p.R334X | NA | No | Pathogenic | 31313072, 12692554, 25662009, 31493092 |
| 43 | CXCR4 | Exon2 | c.1000C>T | p.R334X | NA | No | Pathogenic | 31313072, 12692554, 25662009, 31493092 |
| 44 | CXCR4 | Exon2 | c.1032dupT | p.E345X | De novo | Yes | NA§ | NA§ |
| 45 | CXCR4 | Exon2 | c.1000C>T | p.R334X | De novo | No | Pathogenic | 31313072, 12692554, 25662009, 31493092 |
| 46 | SBDS | Exon2 | c.184A>T | p.K62X | Maternal | No | Pathogenic/likely pathogenic | 33607811 37885353 |
| SBDS | Intron2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 47 | SBDS | Exon2 | c.184A>T | p.K62X | Maternal | No | Pathogenic/likely pathogenic |
33607811 37885353 |
| SBDS | Intron2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 48 | SBDS | Intron2 | c.258+2T>C | splicing | Maternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 |
| SBDS | Intron2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 49 | SBDS | Intron2 | c.258+2T>C | splicing | Maternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 |
| SBDS | Intron2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 50 | SBDS | Exon2 | c.183_184TA>CT | p.K62X | Maternal | No | Pathogenic | 12496757, 15769891, 32412173 |
| SBDS | Exon2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 51 | SBDS | Intron2 | c.258+2T>C | splicing | Maternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 |
| SBDS | Exon2 | c.183_184TA>CT | p.K62X | Paternal | No | Pathogenic | 12496757, 15769891, 32412173 | |
| 52 | SBDS | Exon2 | c.184A>T | p.K62X | Maternal | No | Pathogenic/likely pathogenic |
33607811 37885353 |
| SBDS | Intron2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 53 | SBDS | Exon2 | c.183_184TA>CT | p.K62X | Maternal | No | Pathogenic | 12496757, 15769891, 32412173 |
| SBDS | Intron2 | c.258+2T>C | splicing | Paternal | No | Pathogenic | 12496757, 22935661, 21695142, 14749921 | |
| 54 | WAS | Exon9 | c.881T>C | p.I294T | Maternal | No | Pathogenic/likely pathogenic | 11242115, 19006568 |
| 55 | G6PC3 | Exon3 | c.394C>T | p.Q132X | Maternal | Yes | NA | NA |
| 56 | SPR54 | Exon5 | c.349_351del | p.T117del | De novo | No | Pathogenic | 29914977, 36159802 |
∗
Novel variant denotes that the variant was not reported in the NCBI website ClinVar database and GnomAD database. We also referred to ELANE mutations published previously.15, 16, 17, 18
†
Clinical significance represents the assessment of the variant in the ClinVar database or the predicted pathogenicity using polyphen-2.
‡
Reference PMID represents the number of the reported or referenced literature in Pubmed for the mutation.
§
NA, not available.
‖
Cyclic neutropenia (CyN).
¶
Compound heterozygous mutations. P19 and P20, as well as P28 and P29, are from 2 separate twin families. The father of P19 and P20 has the same compound heterozygous mutations and presented with neutropenia, recurrent respiratory infections, and oral ulcers. P26 inherited the p.C208R variant from his father, whose blood tests were suggestive of neutropenia, although the exact neutrophil count was not recorded.