Table 3.
Identified pathogenic variants from patients with genetic diagnosis and treatments.
| Case | Gene | Accession | Nucleotide | Amino acid | Zygosity (VAF) | ACMG classification | Novel variants? | Disease (MIM#) | Inheritance | Treatment |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | BTK | NM_000061.2 | c.763C>T | p.Arg255Ter | Hemi | Pathogenic | Known | Agammaglobulinemia, X-linked 1 (300755) | XLR | IGRT |
| 2 | UNC13D | NM_199242.2 | c.1055 + 1G>A | – | Hetero | Likely pathogenic | Known | Hemophagocytic lymphohistiocytosis, familial, 3 (608898) | AR | HSCT |
| c.118-308C>T | – | Hetero | Likely pathogenic | Known | ||||||
| 3 | STAT3 | NM_139276.2 | c.1144C>T | p.Arg382Trp | Hetero | Pathogenic | Known | Autoimmune disease, multisystem, infantile-onset, 1 (615952) Hyper-IgE recurrent infection syndrome (147060) |
AD | Antibiotic prophylaxis |
| 4 | STAT3 | NM_139276.2 | c.2144C>T | p.Pro715Leu | Hetero | Likely pathogenic | Known | Autoimmune disease, multisystem, infantile-onset, 1 (615952) Hyper-IgE recurrent infection syndrome (147060) |
AD | Ruxolitinib Steroid |
| 5 | IL2RG | NM_000206.2 | c.681del | p.Phe227LeufsTer46 | Hemi | Likely pathogenic | Novel | Severe combined immunodeficiency, X-linked (300400) | XLR | HSCT |
| 6 | BTK | NM_000061.2 | c.1780G>A | p.Gly594Arg | Hemi | Pathogenic | Known | Agammaglobulinemia, X-linked 1 (300755) | XLR | IGRT |
| 7 | NRAS | NM_002524.4 | c.38G>A | p.Gly13Asp | Hetero | Likely pathogenic | Known | RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic (614470) | – | Conservative care |
| 8 | SH2D1A | NM_002351.4 | c.1A>G | p.Met1? | Hemi | Pathogenic | Novel | Lymphoproliferative syndrome, X-linked, 1 (308240) | XLR | HSCT |
| 9 | GATA2 | NM_001145661.1 | c.1018_1036delinsAATTT | p.Ser340Asnfs*39 | Somatic (11.6%) |
Likely pathogenic | Novel | Immunodeficiency 21 (614172) | AD | HSCT |
| 10 | TET2 | NM_001127208.2 | c.2188del | p.Thr730HisfsTer21 | Somatic (9.2%) |
Likely pathogenic | Novel | Immunodeficiency 75 (619126) | AR | Ganciclovir Bortezomib |
| 11 | PRF1 | NM_001083116.1 | c.65del | p.Pro22ArgfsTer29 | Homo | Pathogenic | Known | Hemophagocytic lymphohistiocytosis, familial, 2 (603553) | AR | HSCT |
| 12 | IL2RG | NM_000206.2 | c.340G>A | p.Gly114Ser | Hemi | Likely pathogenic | Novel | Severe combined immunodeficiency, X-linked (300400) | XLR | HSCT |
| 13 | IL10RA | NM_001558.3 | c.537G>A | p.Thr179= | Hetero | Pathogenic | Known | Inflammatory bowel disease 28, early onset, autosomal recessive (613148) | AR | HSCT |
| NM_001558.3 | Exon 1 deletion | Hetero | Likely pathogenic | Known | ||||||
| 14 | BTK | NM_000061.2 | c.842G>A | p.Trp281Ter | Hemi | Likely pathogenic | Known | Agammaglobulinemia, X-linked 1 (300755) | XLR | IGRT |
| 15 | UBA1 | NM_153280.2 | c.121A>C | p.Met41Leu | Somatic*
(84%) |
Pathogenic | Known | VEXAS syndrome, somatic (301054) | XLR | HSCT |
*This variant was detected from whole blood sample and was not detected from buccal swab sample.
VAF, variant allele frequency; XLR, X-linked recessive; AR, autosomal recessive; AD, autosomal dominant; IGRT, immunoglobulin replacement therapy; HSCT, hematopoietic stem cell transplantation.