Table 3. Patients with previously reported single nucleotide variants, small insertion-deletions, or copy number variants that may (partially) explain the patient’s immunological phenotype.
Listed variants were identified prior to the research-based systematic re-analysis of the current study following diagnostic gene panel analysis for inborn errors of immunity.
| Patient nr. | Sex | Age range at sampling | Phenotype (IUIS classification) | Variant | Mutational mechanism | ACMG classification | ClinVar accession | Comments |
|---|---|---|---|---|---|---|---|---|
| 10 | F | 0–5 | Immune dysregulation, HLH/EBV | AP3B1 Chr5(GRCh37):g.77563371del NM_003664.4:c.177del p.(Lys59fs) | AR (ch) LoF | Pathogenic | VCV000224763 | Hermansky-Pudlak syndrome 2 (OMIM #608233) |
| AP3B1 Chr5(GRCh37):g.77423980_77423983del NM_003664.4:c.1839_1842del p.(Asp613fs) | Pathogenic | VCV000224764 | ||||||
| 12 | F | 11–15 | CID, syndromal | FAS Chr10(GRCh37):g.90774167_90774186dup NM_000043.6:c.968_987dup p.(Glu330fs) | AD (htz) LoF | Pathogenic | VCV000016509 | Autoimmune lymphoproliferative syndrome, type IA (OMIM #601859) |
| seq[GRCh37] del(16)(p11.2p11.2) NC_000016.9:g.(29469093_29624260)_(30199846_30208282)del | AD (htz) LoF | Pathogenic | - | 16 p11.2 deletion syndrome (OMIM #611913) | ||||
| 26 | F | 0–5 | Bone marrow failure | DHFR Chr5(GRCh37):g.79950248C>T NM_000791.3:c.61G>A p.(Gly21Arg) | AR (hmz) LoF | Likely pathogenic | - | Megaloblastic anaemia due to dihydrofolate reductase deficiency (OMIM #613839) Affected sibling carries equal variant |
| 59 | M | 6–10 | Autoinflammatory disorder | NLRP3 Chr1(GRCh37):g.247587794C>T NM_001079821.2:c.1049C>T p.(Thr350Met) | AD (htz) LoF | Pathogenic | - | Muckle-Wells syndrome (OMIM #191900) De novo SNV |
| 61 | M | 0–5 | CID, syndromal | MKL1 Chr22(GRCh37):g.40815086dup NM_020831.4:c.1356dup p.(Val453Argfs) | AR (hmz) LoF | Likely pathogenic | - | Immunodeficiency 66 (OMIM #618847) Affected sibling carries equal variant |
| 77 | F | 0–5 | CID, syndromal | ALOXE3 Chr17(GRCh37):g.8006708G>A NM_021628.2:c.1889C>T p.(Pro630Leu) | AR (hmz) LoF | Pathogenic | - | Congenital ichthyosis 3 (OMIM #606545) |
| 91 | F | 0–5 | Suspected SCID (low TRECs) | FOXN1 Chr17(GRCh37):g.26857765A>G NM_003593.2:c.831–2A>G p.? | AD (htz) LoF | Likely pathogenic | - | T-cell lymphopenia, infantile, with or without nail dystrophy (OMIM #618806) |
| 102 | F | 11–15 | Immune dysregulation, autoimmunity and others | CD55 Chr1(GRCh37):g.207497984dup NM_001300902.1:c.367dup p.(Thr123fs) | AR (hmz) LoF | Pathogenic | - | Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (OMIM #226300) |
| PET117 Chr20(GRCh37):g.18122927C>T NM_001164811.1:c.172C>T p.(Gln58*) | AR (hmz) LoF | Likely pathogenic | VCV000981504 | Mitochondrial complex IV deficiency, nuclear type 19 (OMIM #619063) | ||||
| 105 | M | 31–35 | Defects in intrinsic and innate immunity, MSMD and viral infection | TLR7 ChrX(GRCh37):g.12905756_12905759del NM_016562.3:c.2129_2132del p.(Gln710fs) | XLR (hemi) LoF | Pathogenic | VCV000977232 | Immunodeficiency 74, COVID19-related (OMIM #301051) Affected sibling carries equal variant |
| 114 | M | 6–10 | Immune dysregulation, autoimmunity and others | LRBA Chr4(GRCh37):g.151835415del NM_006726.4:c.1093del p.(Tyr365fs) | AR (hmz) LoF | Pathogenic | - | Common variable immunodeficiency 8 (OMIM #614700) |
| 120 | M | 11–15 | Congenital defect of phagocyte, functional defects | NCF1 Chr7(GRCh37):g.74191615_74191616del NM_000265.5:c.75_76del p.(Tyr26fs) | AR (hmz) LoF | Pathogenic | VCV000002249 | Chronic granulomatous disease 1 (OMIM #233700) |
| 122 | M | 0–5 | Suspected SCID (low TRECs) | FOXN1 Chr17(GRCh37):g.26851540del NM_003593.2.1:c.143del p.(Cys48fs) | AD (htz) LoF | Pathogenic | - | T-cell lymphopenia, infantile, with or without nail dystrophy (OMIM #618806) |
Abbreviations: IUIS = International Union of Immunological societies; ACMG = American College of Medical Genetics and Genomics; HLH = haemophagocytic lymphohistiocytosis; EBV = Epstein-Barr virus; OMIM = Online Mendelian Inheritance in Man; (S)CID = (severe) combined immunodeficiency; TREC = T cell receptor excision circle; MSMD = Mendelian susceptibility to mycobacterial disease; AR = autosomal recessive; AD = autosomal dominant; XLR = X-linked recessive; ch = compound heterozygous; htz = heterozygous; hmz = homozygous; hemi = hemizygous; LoF = loss-of-function; SNV = single nucleotide variant.