Summary of patient phenotypes including main clinical manifestations and laboratory features in 4 patients harboring missense variant CXCR4D84H
| . | P1 . | P2∗ . | P3 . | P4 . | Reference ranges . | ||
|---|---|---|---|---|---|---|---|
| Characteristics | |||||||
| CXCR4 variant | c.250G>C (p.D84H) heterozygous | c.250G>C (p.D84H) heterozygous | c.250G>C (p.D84H) heterozygous | c.250G>C (p.D84H) heterozygous | |||
| Sex at birth | Female | Male | Male | Female | |||
| Age, y | 40 | 13 | 3, died | 67 | |||
| Hemogram, ×109/L† | 1-6 y | 12-18 y | 18+ y | ||||
| WBC | 2.2-3.9 | 0.68-6.03 | 13.3 | 8.08 | 5.0-17.0 | 4.5-13.0 | 3.2-9.8 |
| Neutrophils | 0.6-1.2 | 0.16-2.79 | 8.9 | 4.93 | 1.0-8.5 | 1.5-8.0 | 1.56-6.45 |
| Lymphocytes | 1.5-2.1 | 0.43-2.55 | 2.9 | 2.49 | 1.5-9.5 | 1.1-4.5 | 0.95-3.07 |
| Monocytes | 0-0.1 | 0.07-0.52 | 1.07 | 0.5 | 0.2-1.0 | 0.2-1.0 | 0.24-0.86 |
| Platelets | 144-166 | 53-268 | 54 | 298 | 150-400 | 150-400 | 150-450 |
| Serum immunoglobulin, mg/dL‡ | 2 to <4 y | 10 to <13 y | 18+ y | ||||
| IgG | 1060 | 650 | 858-982 | 403 | 295-1156 | 503-1719 | 767-1590 |
| IgG1 | § | § | § | 200 | 158-721 | 280-1030 | 341-894 |
| IgG2 | § | § | § | 156 | 39-176 | 66-502 | 171-632 |
| IgG3 | § | § | § | 37 | 17-84.7 | 11.5-105.3 | 18.4-106 |
| IgG4 | § | § | § | 5.2 | 0.4-49.1 | 1.0-121.9 | 2.4-121.0 |
| IgM | 109 | 54 | 67-81 | 81 | 27-246 | 42-295 | 61-356 |
| IgA | 94 | 162 | 61-98 | 98 | 37-184 | 41-255 | 37-278 |
| Tetanus antibody titer, IU/mL | 5.22 | § | § | 1.41 | >0.16 | >0.16 | |
| Pneumococcal antibody titers, μg/mL | 21/23 serotypes >1.3 | § | § | § | >1.3 | >1.3 | |
| Clinical presentation | |||||||
| Bone marrow | Hypocellular (20%-30%) with mild granulocytic hypoplasia, hypolobulated megakaryocytes, bilobed neutrophils, and granulocyte precursors | Increased cellularity, 64% of cells are represented by neutrophils of varying degrees of maturity | ITP; punctate is rich; there are many megakaryocytes, but no functioning | § | |||
| Warts | Hands, feet, and anogenital | (−) | (−) | (−) | |||
| Infections | EBV, HPV, and H1N1 pneumonia | HSV, parvovirus, SARS-CoV-2, pneumonia (Bacillus cereus, Pseudomonas species), and diarrhea (Candida) | Seroconverted for CMV and EBV, HSV | URTI | |||
| Malignancy | Anal intraepithelial neoplasia grade 3, cervical carcinoma in situ, high-grade vulval intraepithelial neoplasia, and anal dysplasia | (−) | (−) | (−) | |||
| Other | Autoimmune thyroiditis | ||||||
| Prior treatments | |||||||
| Immunoglobulin therapy | (−) | (+) | (+) | (+) | |||
| G-CSF | (−) | (−) | (−) | (−) | |||
| Antibiotics | Rare | (+) | (+) | (+); prophylaxis | |||
| Other | Cidofovir for AIN3 | ||||||
| Family history | Family members decline genetic testing. No clinically affected family members | Mother harbors D84H; healthy | Not known | (−) | |||
| . | P1 . | P2∗ . | P3 . | P4 . | Reference ranges . | ||
|---|---|---|---|---|---|---|---|
| Characteristics | |||||||
| CXCR4 variant | c.250G>C (p.D84H) heterozygous | c.250G>C (p.D84H) heterozygous | c.250G>C (p.D84H) heterozygous | c.250G>C (p.D84H) heterozygous | |||
| Sex at birth | Female | Male | Male | Female | |||
| Age, y | 40 | 13 | 3, died | 67 | |||
| Hemogram, ×109/L† | 1-6 y | 12-18 y | 18+ y | ||||
| WBC | 2.2-3.9 | 0.68-6.03 | 13.3 | 8.08 | 5.0-17.0 | 4.5-13.0 | 3.2-9.8 |
| Neutrophils | 0.6-1.2 | 0.16-2.79 | 8.9 | 4.93 | 1.0-8.5 | 1.5-8.0 | 1.56-6.45 |
| Lymphocytes | 1.5-2.1 | 0.43-2.55 | 2.9 | 2.49 | 1.5-9.5 | 1.1-4.5 | 0.95-3.07 |
| Monocytes | 0-0.1 | 0.07-0.52 | 1.07 | 0.5 | 0.2-1.0 | 0.2-1.0 | 0.24-0.86 |
| Platelets | 144-166 | 53-268 | 54 | 298 | 150-400 | 150-400 | 150-450 |
| Serum immunoglobulin, mg/dL‡ | 2 to <4 y | 10 to <13 y | 18+ y | ||||
| IgG | 1060 | 650 | 858-982 | 403 | 295-1156 | 503-1719 | 767-1590 |
| IgG1 | § | § | § | 200 | 158-721 | 280-1030 | 341-894 |
| IgG2 | § | § | § | 156 | 39-176 | 66-502 | 171-632 |
| IgG3 | § | § | § | 37 | 17-84.7 | 11.5-105.3 | 18.4-106 |
| IgG4 | § | § | § | 5.2 | 0.4-49.1 | 1.0-121.9 | 2.4-121.0 |
| IgM | 109 | 54 | 67-81 | 81 | 27-246 | 42-295 | 61-356 |
| IgA | 94 | 162 | 61-98 | 98 | 37-184 | 41-255 | 37-278 |
| Tetanus antibody titer, IU/mL | 5.22 | § | § | 1.41 | >0.16 | >0.16 | |
| Pneumococcal antibody titers, μg/mL | 21/23 serotypes >1.3 | § | § | § | >1.3 | >1.3 | |
| Clinical presentation | |||||||
| Bone marrow | Hypocellular (20%-30%) with mild granulocytic hypoplasia, hypolobulated megakaryocytes, bilobed neutrophils, and granulocyte precursors | Increased cellularity, 64% of cells are represented by neutrophils of varying degrees of maturity | ITP; punctate is rich; there are many megakaryocytes, but no functioning | § | |||
| Warts | Hands, feet, and anogenital | (−) | (−) | (−) | |||
| Infections | EBV, HPV, and H1N1 pneumonia | HSV, parvovirus, SARS-CoV-2, pneumonia (Bacillus cereus, Pseudomonas species), and diarrhea (Candida) | Seroconverted for CMV and EBV, HSV | URTI | |||
| Malignancy | Anal intraepithelial neoplasia grade 3, cervical carcinoma in situ, high-grade vulval intraepithelial neoplasia, and anal dysplasia | (−) | (−) | (−) | |||
| Other | Autoimmune thyroiditis | ||||||
| Prior treatments | |||||||
| Immunoglobulin therapy | (−) | (+) | (+) | (+) | |||
| G-CSF | (−) | (−) | (−) | (−) | |||
| Antibiotics | Rare | (+) | (+) | (+); prophylaxis | |||
| Other | Cidofovir for AIN3 | ||||||
| Family history | Family members decline genetic testing. No clinically affected family members | Mother harbors D84H; healthy | Not known | (−) | |||
Values not within the normal range are shown in bold font.
AIN3, anal intraepithelial neoplasia grade 3; CMV, cytomegalovirus; EBV, Epstein-Barr virus; G-CSF, granulocyte colony-stimulating factor; H1N1, influenza A virus subtype H1N1; HPV, human papillomavirus; HSV, herpes simplex virus; ITP, immune thrombocytopenia; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; URTI, upper respiratory tract infection; WBC, white blood cell.
The range for P2 is based on 2 different time points: 2020 and 2021.
Hemogram reference ranges for <18 years and >18 years of age are based on cutoffs provided by North Bristol National Health Service and Cleveland Clinic, respectively.
Serum immunoglobulin references ranges are based on cutoffs provided by Mayo Clinic Laboratories.
No data.