Table 1.
Variant detail of patients with various IEI and corresponding flow-cytometry results.
| S. No | Age | Sex | Clinical presentation | Diagnosis | Inheritance | Zygosity | Gene | Transcript ID | Exon | Variation | Variant effect | CADD Score | ACMG Classification | Flow-cytometry results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 18 years | M | Monoarthritis | XLA | XL | Hemizygous | BTK | NM_000061.2 | 18 | p.Arg618Gly | Missense | 25.8 | Likely Pathogenic (PM1, PM2, PP2, PP3) |
Btk Protein Expression on gated CD14 + monocytes Control-83.23% SI 3.16 Patient-00.66% SI 1.03 |
| 2 | 11 years | M | Ompahlitis, diarrhea, Leukopenia | XLA | XL | Hemizygous | BTK | NM_000061.2 | 18 | p.Gly594Glu | Missense | 26.6 | Likely Pathogenic (PM1, PM2, PM5, PP2, PP3) | B lymphocyte; 0.03% |
| 3 | 5 years | M | Diarrhea, Bronchiectasis, pyogenic meningitis | XLA | XL | Hemizygous | BTK | NM_000061.2 | 16 | p.Arg544Met | Missense | 34 | Pathogenic (PVS1, PM1, PM2, PM5, PP2, PP3) |
Btk Protein Expression on gated CD14 + monocytes Control-60.78%SI 4.4 Patient 3.88% 2.8 |
| 4 | 8 months | M | XLA | XL | Hemizygous | BTK | NM_000061.2 | 2 | p.Leu37Pro | Missense | 26.2 | Likely Pathogenic (PM1, PM2, PP2, PP3) | – | |
| 5 | 16 years | M | Pneumonia, Diarrhea, Measles, hepatitis, seizures | XLA | XL | Hemizygous | BTK | NM_000061.2 | 6 | p.Gly173Glufs*3 | Frameshift | - | Pathogenic (PVS1, PM2, PP3) |
B cells : 0.02% Btk Protein Expression on gated CD14 + monocytes Control-99.45% SI 28.6 Patient-83.33%. SI 6.8 |
| 6 | 8 years | M | Pneumonia, Bronchiectasis | XLA | XL | Hemizygous | BTK | NM_000061.2 | 16 | c.1567-2A > C | Splice-site | 34 | Pathogenic (PVS1, PM2, PP3) |
CD3/19 + = 79.64/0.56%, BTK protein expression on monocytes = Control-98.73% SI 17.6 Patient-91.49% SI 10.8 |
| 7 | 11 years | M | X-linked family history (two maternal uncles death) | XLA | XL | Hemizygous | BTK | NM_000061.2 | 8 | p.Arg255* | Nonsense | 35 | Pathogenic (PVS1, PP5, PM2, PP3) |
B cells; 0.09% Btk Protein Expression on gated CD14 + monocytes Control 68.74% SI 6.8 Patient 2.37%. SI 1.8 |
| 8 | 1 years | M | Maternal cousin died of XLA, 2 episodes of febrile seizure | XLA | XL | Hemizygous | BTK | NM_000061.2 | Deletion Exon 10,11 | Large Deletion | – | Pathogenic |
B cells: 0.47% Btk expression on CD14 + monocytes Control:98% SI 7.0 Control:91% SI 2.9 |
|
| 9 | 9 months | M | Cutaneous abscess, pneumonia, lung abscess, cervical adenitis, | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 12 | p.Trp516Arg | Missense | 27.6 | Likely Pathogenic (PM2, PM5, PP2, PP3, PP5) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 93.35% SI 103 Patient 0.59%. SI 1.0 |
| 10 | 11 years | F | Skin abscess, pneumonia, Osteomyelitis | CGD | AR | Homozygous | NCF2 | NM_001127651.2 | 9 | p.Thr279Glyfs*16 | Frameshift | - | Pathogenic (PVS1, PM2, PP3, PP5) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 97.97%. SI 121 Patient 17.57%. SI 2.26 |
| 11 | 3 months | M | CGD | AR | Homozygous | NCF2 | NM_001127651.2 | 9 | p.Thr279Glyfs*16 | Frameshift | - | Pathogenic (PVS1, PM2, PP3, PP5) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 95.10%. SI 118.6 Patient 13.93%. SI. 1.3 |
|
| 12 | 1 years | M | Septicemia, pneumonia | CGD | XL | Hemizygous | CYBB | NM_000397.3 | IVS10 | c.1152-1G > A | Splice-site | 34 | Pathogenic (PVS1, PM2, PP3, PP5) | – |
| 13 | 4 years | M | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 5 | p.Glu150* | Nonsense | 35 | Pathogenic (PVS1, PM2, PP3, PP5) | – | |
| 14 | 3 months | M | Pneumonia, cervical adenitis, liver abscess- multiloculated, Septicemia | CGD | AR | Homozygous | NCF2 | NM_001127651.2 | 9 | p.Thr279Glyfs*16 | Frameshift | – | Pathogenic (PVS1, PM2, PP3, PP5) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 97.26% SI 97.8 Patient 1.23%. SI 3.9 |
| 15 | 8 years | M | Pneumonia, submandibular adenitis | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 7 | p.Gly252Glufs*31 | Frameshift | Pathogenic (PVS1, PM2, PP3) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 89.94% SI 94.2 Patient 38.71% SI 3.2 b558 expression on Granulocyte = Control-98.21%, Patient-03.00% |
|
| 16 | 7 months | M | Cervical lymphadenitis, multiple abscess | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 12 | p.Asp500Asn | Missense | 27.9 | Likely Pathogenic (PM2, PM5, PP2, PP3) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 96.92%, SI 137.7 Patient 86.16%. SI 7.7 |
| 17 | 1 months | M | Fever, abdominal distension, sepsis meningitis, pneumonia | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 11 | p.Trp443* | Nonsense | 41 | Pathogenic (PVS1, PM2, PP3) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 99.47% SI 230.4 Patient 12.75%. SI 1.8 |
| 18 | 9 months | M | Fever,PUO, Pyonephrosis, pneumonia | CGD | AR | Homozygous | NCF2 | NM_001127651.2 | 9 | p.Thr279Glyfs*16 | Frameshift | – | Pathogenic (PVS1, PM2, PP3, PP5) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 99.61% SI 272.4 Patient 37.35%. SI 2.7 |
| 19 | 1.5 years | M | Axillary adenitis, pneumonia, skin abscess, BCG adenitis, osteomyelitis of right foot | CGD | AR | Compound Heterozygous | NCF2 | NM_001127651.2 | 13 | p.His389Gln, c.1178 + 1G > A | Missense, Splice-site | 22.8, 34 |
Benign (BA1, BP6, BP1); Pathogenic (PVS1, PM2, PP3, PP5) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 97.81% SI 126.3 Patient 00.98%. SI 0.9 |
| 20 | 3 months | M | Abscess in right sub mandibular, pneumonia,lymphadenitis, | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 1 | p.Met1Arg | Missense | 26.4 | Pathogenic (PVS1, PM2, PP3) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 95.13% SI 183.8 Patient 19.93% SI 1.5 Expression of b558 on Granulocytes = Control-66.50% Patient-11.5% |
| 21 | 2 months | M | Pneumonia, lymphadenitis, abscess, ear discharge, otitis, scalp rash, GI bleed | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 9 | p.Val321Serfs*27 | Indel | – | Pathogenic (PVS1, PM2, PP3) |
Dihydrorhodamine assay (% of neutrophils showing oxidase activity) Control 87.40% SI 32.5 Patient 00.64% SI 1.0 b558 expression on Granulocyte = Control-96.36% SI 6.8 Patient-07.64%. SI 1.2 |
| 22 | 2 years | M | Pneumonia , lymphadenitis, neck abscess | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 9 | p.Ile325Phe | Missense | 25.2 | Likely Pathogenic (PM1, PM2, PP2, PP3, PP5) |
DHR SI = Control 96.2%. SI 63.77 Patient 70.5%. SI 5.27 b558 expression on neutrophils Control 98% SI 9.0 Patient 3% SI 1.1 |
| 23 | 2 years | M | Abscess in left gluteal region, liver abscess | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 8 | p.Arg290* | Nonsense | 35 | Pathogenic (PVS1, PM2, PP5, PP3) |
DHR = Control 93.66% Patient 0.07% |
| 24 | 5 months | M | Pneumonia, fever and cough | CGD | AR | Homozygous | NCF2 | NM_001127651.2 | 9 | p.Thr279Glyfs*16 | FrameshiftDeletion | – | Pathogenic (PVS1, PM2, PP3, PP5) |
DHR = Control 99.25% SI 34 Patient 49.69%. SI 0.8 B558 expression on granulocytes Control 68% SI 6.3 Patient. 0.5% SI 1.2 |
| 25 | 7 years | M | Burkholderia sepsis, pneumonia, lymphadenitis, colitis | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 9 | p.Glu309Lys | Missense | 28.1 | Likely Pathogenic (PM1, PM2, PP5, PP2, PP3) |
DHR SI = Control 97% SI 101.99 Patient 88%. SI. 11.44 b558 expression on granulocytes Control 99% SI 9.7 Patient 71% SI 4.5 |
| 26 | 8 months | M | Colitis, nasal granuloma, Septicemia, diarrhea, hypergammaglobulinemia | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 6 | p.Ile190_Thr191del | Nonframeshift Deletion | – | Likely Pathogenic (PM1, PM2, PM4, PP3) |
DHR = Control 99.51% SI 158.7 Patient- 4.64% SI 1.9 Expression of b558 on Granulocytes = Control-97.84% SI 14.2 Patient-00.25% SI 1.2 Mother-38.68% |
| 27 | 8 months | M | Ear discharge, blood in stools, pneumonia, allergic proctitis | CGD | AR | Homozygous | CYBA | NM_000631.4 | Deletion Exon 2–4 | Large Deletion | – | Pathogenic | – | |
| 28 | 1 year | M | Pneumonia, cervical lymphadenitis | CGD | XL | Hemizygous | CYBB | NM_000397.3 | 5 | p.Arg130* | Nonsense | 34 | Pathogenic (PVS1, PM2, PP5, PP3) |
DHR = Control 99.91% SI 161 Patient 4.65% SI 1.42 Expression of b558 on Granulocytes = Control-79.22% SI 2.7 Patient-00.2%. SI 0.7 |
| 29 | 4 months | M | CGD | AR | Homozygous | NCF2 | NM_001127651.2 | 3 | p.Arg66* | Nonsense | 36 | Pathogenic (PVS1, PM2, PP3, PP5) |
DHR Control 85% SI 87 Patient 0.15% Si 0.98 |
|
| 30 | 2.5 months | F | Rash pneumonia, diarrhea, Purulent ear discharge, oral thrush, hepatosplenomegaly | SCID | AR | Homozygous | RAG2 | NM_001243786.1 | 3 | p.Trp416Leu | Missense | 27.7 | Likely Pathogenic (PM1, PM2, PP2, PP3) |
Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 7.67/0.69/82.67/0.35 CD4/CD8 ratio = Con-2.20; Pt-7.81 CD45RA + = Con-63.64%, Pt. 06.42% CD4 + CD45RA + = Con-58.06%, Pt-10.20% CD8 + CD45RA + = Con-82.31%, Pt-04.18% |
| 31 | 5 months | M | Pneumonia, absent thymus, candida sepsis (blood, urine), BAL- Pseudomonas | SCID | AR | Homozygous | RAG1 | NM_000448.2 | 2 | p.Arg716Gln | Missense | 31 | Likely Pathogenic (PM1, PM2, PM5, PP2, PP3, PP5) | Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 2.36/3.84/92.22/1.21% |
| 32 | 1 months | F | Rash, Pneumonia, nephrotic syndrome, Failure to thrive | SCID | AR | Homozygous | ADA | NM_000022.2 | 5 | p.Gly136Asp | Missense | 25.7 | Likely Pathogenic (PM1, PM2, PP2, PP3) | Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 89.01/0.33/0.77/3.37% |
| 33 | 8 months | F | Pneumonia, hepatosplenomegaly, failure to thrive, diarhhoea, Blood Acetobacter baumanii | SCID | AR | Compound Heterozygous | JAK3 | NM_000215.3 | 8,6 | p.Arg350Trp, p.Met235Thr | Missense | 31, 24.2 |
Likely Pathogenic (PM1,PM2, PP2, PP3); Uncertain Significance (PM1, PM2, PP2) |
Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 11.32/69.81/1.75/14.86% CD127 Control-59.18, Patient-5.14, |
| 34 | 4 years | M | Multiple episodes of pneumonia | SCID | AR | Homozygous | ADA | NM_000022.2 | IVS6 | c.478 + 6 T > A | Splice-site | 24.4 | Likely Pathogenic (PM2, PP3) |
Lymphocyte Subset (CD3/20 +)% = 64.75/03.91% HLA DR + on CD3 T cells = Control-12.60%, Patient-91.96% CD4/CD8 ratio = Con-1.47; Pt-00.06 CD45RO + = Con-65.22%, Pt. 23.39% CD4 + CD45RO + = Con-64.15%, Pt-16.44% CD8 + CD45RO + = Con-72.60%, Pt-17.30% |
| 35 | 3 years | M | Consanguinity, family history, pneumonia, failure to thrive, rash, diarrhea, absent thymus | SCID | AR | Compound Heterozygous | RAG1 | NM_000448.2 | 2 | p.Glu193Lys, p.Lys621Argfs*10 | Missense, Frameshift | 17.71, - |
Benign (PP2, PP3, BS1, BS2, BP6); Pathogenic (PVS1, PM2, PP3) |
Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 59.82/2.25/15.06/18.94% |
| 36 | 35 days | M | Pneumonia, diarrhea, failure to thrive, | SCID | AR | Homozygous | RAG1 | NM_000448.2 | 2 | p.Gly393Alafs*10 | Frameshift | – | Pathogenic (PVS1, PM2, PP3) | – |
| 37 | 8 months | M | Family history, rash, pneumonia, diarrhea, failure to thrive | SCID | XL | Hemizygous | IL2RG | NM_000206.2 | 5 | p.Ser251* | Nonsense | 34 | Likely Pathogenic (PVS1, PM2, BP4) |
Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 1.37/96.34/0.90/0.50% , Expression of CD132 on L/M/N = Control-48.25/81.71/77.48, Patient-24.27/25.84/26.82%, HLA DR + T-cells = Control-15.71%, Patient-83.46%, CD4/CD8 ratio = Con-0.92; Pt-1.37 CD45RA + = Con-48.96%, Pt. 5.93% CD4 + CD45RA + = Con-42.39%, Pt-1.23% CD8 + CD45RA + = Con-56.99%, Pt-10.19% |
| 38 | 9 months | M | Family history, diarrhea | SCID | AR | Homozygous | ADA | NM_000022.2 | 9 | p.Arg282Leu | Missense | 35 | Pathogenic (PVS1, PM1, PM2, PM5, PP2, PP3) | Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 53.18/1.54/24.35/13.28% |
| 39 | 6 months | M | Severe pneumonia, death in neonatal period | SCID | XL | Hemizygous | IL2RG | NM_000206.2 | 2 | p.Leu57His | Missense | 25.5 | Likely Pathogenic (PM2, PP2, PP3) | – |
| 40 | 6 months | M | Fever, rash, diarrhea, pneumonia, HLH, pancytopenia, family history | SCID | XL | Hemizygous | IL2RG | NM_000206.2 | 7 | c.924 + 1G > A | Splice-site | 33 | Pathogenic (PVS1, PM2, PP3, PP5) | Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 2.46/87.07/2.51/00.64% |
| 41 | 5.5 months | M | Fever, diarrhea, pneumonia, maculopapular rash, BCG site abscess, cytopenia | SCID | AR | Homozygous | JAK3 | NM_000215.3 | 8 | p.Arg350Trp | Missense | 32 | Likely Pathogenic (PM1, PM2, PP2, PP3) | Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 2.52/93.25/00.41/00.57% |
| 42 | 5 months | M | Rash, pneumonia, hepatosplenomegaly, BCG ulceration, failure to thrive, oral thrush | SCID | XL | Hemizygous | IL2RG | NM_000206.2 | 5 | p.Glu199Valfs*76 | Indel | 36 | Pathogenic |
Lymphocyte Subset (CD3/19/56/3 + 56 +)% = 00.61/97.82/0.22/0.04% Common y chain(CD132) expression on L/M/N = Control-83.53/99.54/66.25% Patient-25.23/98.19/17.53% |
| 43 | 3 months | M | Delayed separation of cord, Omphalitis, Fever, Periumblical erythema, recurrent infections, neutrophilic leukocytosis, thrombocytosis | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 14 | p.Arg693* | Nonsense | 43 | Pathogenic (PVS1, PM2, PP3, PP5) |
CD18 on Granulocyte: Control 98.56% Patient 00.18% |
| 44 | 27 days | M | Swelling and redness around umblicus, Erythema around umblicus, omphalitis, necrotizing fasciitis, neutrophilic leukocytosis | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 14 | p.Arg693* | Nonsense | 43 | Pathogenic (PVS1, PM2, PP3, PP5) |
CD18 on Granulocyte : Control 98.56% Patient 00.15% |
| 45 | 5 months | F | Fluid filled veicle over left thigh erythema, fever, lethargy, peeling of skin, history of loose stools, splenomegaly, sepsis, Ulcer, fever, pallor, thrombocytopenia | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 14 | p.Arg693* | Nonsense | 43 | Pathogenic (PVS1, PM2, PP3, PP5) |
CD18 on Granulocyte : Control 99.93% Patient 00.02% |
| 46 | 6 years | M | Ulcer over left thigh, boil over left gluteal region, fever, single fissure present over groin hypopigmented scar, hyperlinearity of palms, edema | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | c.1224 + 4A > G | Splice-site | 18.96 | Likely Pathogenic (PM2, PP3) |
CD18 on Granulocyte: Control 99.56% Patient 3.60% |
|
| 47 | 4 months | F | Omphalitis, nodule like lesion in perianal area, recurrent febrile, Neutrophilic leucocytosis TLC markedly increased, Microcytic hypochromic anemia, hepatomegaly | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 7 | p.Leu275Alafs*39 | Frameshift | - | Pathogenic (PVS1,PM2) |
CD18 on Granulocyte: Control 99.33% Patient 0.10% |
| 48 | 11 days | F | Neutrophilic leukocytosis, Fever | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 12 | p.Cys506Alafs*23 | Frameshift | - | Pathogenic (PVS1,PM2) |
CD18 on Granulocyte: Control 99.24% Patient 0.00% |
| 49 | 2 months | M | Abdominal distention and persistant leukocytosis, Omphalitis, Neutrophilia | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 14 | p.Arg693* | Nonsense | 43 | Pathogenic (PVS1, PM2, PP3, PP5) |
CD18 on Granulocyte: Control 97.70% Patient 0.06% |
| 50 | 10 days | M | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 7 | c.897 + 1G > A | Splice-site | 24.7 | Pathogenic (PVS1, PM2, PP3, PP5) |
CD18 on Granulocyte: Control 99.88% Patient 01.51% |
|
| 51 | 3 months | M | Fever, loose stools, cough, Oral ulcers, Oral thrush, Umblical cord not fallen, perianal ulcer | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 13 | p.Glu614* | Nonsense | 37 | Pathogenic (PVS1, PM2, PP3) |
CD18 on Granulocyte: Control 96.10% Patient 00.11% |
| 52 | 1 month | F | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 8 | p.Ile316Lysfs*11 | Frameshift | – | Pathogenic (PVS1, PM2, PP3) |
CD18 on Granulocyte: Control 99.89% Patient 00.27% |
|
| 53 | 1 month | M | LAD | AR | Homozygous | ITGB2 | NM_001127491.2 | 14 | c.1878-1G > A | Splice-site | 24 | Pathogenic (PVS1, PM2, PP3) |
CD18 on Granulocyte: Control 99.43% Patient 00.96% |
|
| 54 | 7 years | F | Oculomotor apraxia | Ataxia telangiectasia | AR | Homozygous | ATM | NM_000051.3 | 46 | p.Gln2220* | Nonsense | 40 | Pathogenic (PVS1, PP5, PM2, PP3) | AFP- 178 |
| 55 | 3 years | F | Oculomotor apraxia | Ataxia telangiectasia | AR | Homozygous | ATM | NM_000051.3 | 2 | p.Arg23* | Nonsense | 36 | Pathogenic (PVS1, PP5, PM2, PP3) | AFP- 52.68 |
| 56 | 9 years | M | Oculomotor apraxia, Neuroregression, | Ataxia telangiectasia | AR | Compound Heterozygous | ATM | NM_000051.3 | 24, 50 |
p.Asn1183Trpfs*16, p.Arg2486* |
Frmashift Deletion, Nonsense | 39 | Pathogenic (PVS1, PP5, PM2, PP3) | AFP- 286.3 |
| 57 | 2 years | F | Oculomotor apraxia, Ataxia, telangiectasia | Ataxia telangiectasia | AR | Homozygous | ATM | NM_000051.3 | 2 | p.Arg23* | Nonsense | 36 |
Pathogenic (PVS1, PP5, PM2, PP3) |
AFP- 309 |
| 58 | 8 years | F | Oculomotor apraxia, ocular telangiectasia | Ataxia telangiectasia | AR | Homozygous | ATM | NM_000051.3 | 42 | p.Arg2034* | Nonsense | 37 | Pathogenic (PVS1, PP5, PM2, PP3) | AFP- 611.9 |
| 59 | 6 years | F | Oculomotor apraxia, Tonsilitis | Ataxia telangiectasia | AR | Compound Heterozygous | ATM | NM_000051.3 | 2, 20 | p.Arg23*, c.3077 + 1G > T | Nonsense, Splice-site | 36, 35 | Pathogenic (PVS1, PM2, PP3, PP5) | AFP- 123.38 |
| 60 | 9 years | F | Cerebral atrophy | Ataxia telangiectasia | AR | Compound Heterozygous | ATM | NM_000051.3 | 3 |
p.Arg35*, c.497-6 T > TC |
Nonsense, Splice-site | 34 |
Pathogenic (PVS1, PP5, PM2, PP3); Uncertain Significance (PM2, BP4) |
AFP- 538 |
| 61 | 2 years | M | Oculomotor apraxia | Ataxia telangiectasia | AR | Compound Heterozygous | ATM | NM_000051.3 | 37,49 |
p.Phe1877Leufs*39 p.Arg2436Lys |
Framshift,Missense | 33 |
Uncertain Significance (PM2, PP2, BP4); Pathogenic (PVS1, PM1, PM2, PP2, PP3) |
AFP- 146 |
| 62 | 10 years | M | Gut abnormality, Ataxia, ocular telangiectasia, cerebellar atrophy, recurrent sinopulmonary infections | Ataxia telangiectasia | AR | Compound Heterozygous | ATM | NM_000051.3 | 37, 49 |
p.Phe1877Leufs*39 p.Arg2436Lys |
Framshift,Missense | 33 |
Uncertain Significance (PM2, PP2, BP4); Pathogenic (PVS1, PM1, PM2, PP2, PP3) |
AFP- 566 |
| 63 | 1 year | M | Pneumonia, diarrhea, eczema, skin bleed, family history | WAS | XL | Hemizygous | WAS | NM_000377.2 | 12 | p.*503Argext*79 | Stop-loss | 20.5 | Likely Pathogenic (PM2, PM4) |
WAS Protein expression: Control 99.77% Patient 99.88% |
| 64 | 1 year 2 months | M | WAS | XL | Hemizygous | WAS | NM_000377.2 | p.Arg321* | Nonsense | 33 | Pathogenic (PVS1, PM2, PP5, PP3) | – | ||
| 65 | 11 years | M | AR Hyper IgE | AR | Homozygous | DOCK8 deficiency | NM_203447.3 | 23 | p.Ser948* | Nonsense | 38 | Pathogenic (PVS1, PM2, PP3) | – | |
| 66 | 3 years | M | Recurrent pneumonia, skin infections, eczema, coarse facis | Hyper IgE | AD | Heterozygous | STAT3 | NM_139276.2 | 16 | p.Ile467Phe | Missense | 28.6 | Likely Pathogenic (PM2, PP2, PP3) |
STAT3 Expression: Control-59%, Patient-53.7% Th17 Expression: Control- 0.6%, Patient-0.2% |
| 67 | 8 years | M | Chronic eczema, recurrent cold abscess, NIH score 31, | Hyper IgE | AD | Heterozygous | STAT3 | NM_139276.2 | 14 | p.Arg423Gln | Missense | 32 | Likely Pathogenic (PM2, PP5, PP2, PP3) | STAT3 expression was reduced in patient |
| 68 | 9 years | F | Coarse facial features, crowding of teeth, multiple soft tissue abscess, pneumonia, meningitis | HIGE | AD | Heterozygous | STAT3 | NM_139276.2 | 22 | p.Phe710Ser | Missense | 32 | Likely Pathogenic (PM1, PM2, PP2, PP3) | Reduced Th17 cells in patient |
| 69 | 6 years | M | Multifocal non-tubercular mycobacterial osteitis | MSMD | AD | Heterozygous | IFNGR1 | NM_000416.2 | 6 | p.Asn274Hisfs*2 | Frameshift | - | Pathogenic (PVS1, PP5, PM2) |
CD119 Expression = Control-100% Patient-97.7% |
| 70 | 5 years | F | Disseminated Tuberculosis with multifocal osteomyelitis | MSMD | AR | Homozygous | IFNGR1 | NM_000416.2 | 1 | p.Met1Ile | Missense | 24.1 | Pathogenic (PVS1, PM2, PP3) |
Expression of CD119(IFN-γR1) on Granulocyte/Monocyte/Lymphocyte: Control-99.40,98.86,89.38% Patient-44.78,06.97,08.71% |
| 71 | 8 months | F | Abdominal distension, fever, non healing left axillary ulcer, multiple swelling of axillary, neck and B/L inguinal region, Pallor, Supparative lymphadenitis | MSMD | AR | Homozygous | IL12RB1 | NM_001290024.1 | 14 | c.1738 + 2T > A | Splice-site | 33 | Pathogenic (PVS1, PM2, PP3) |
Expression of CD212 (IL12R-β1) = Control-48.09%, Patient-7.45% |
| 72 | 8 years | M | Fever, diarrhea, multiple infections, oral thrush | GATA2 | AD | Heterozygous | GATA2 | NM_032638.4 | 2 | p.Arg67Serfs*10 | Frameshift | - | Pathogenic (PVS1, PM2, PP3) | Reduced B-cells |
| 73 | 6 years | M | ALPS | AD | Heterozygous | FAS | NM_000043.4 | 3 | p.Gly66Asp | Missense | 25.6 | Likely Pathogenic (PP3, PM1, PM2, PP2) | Double negative T lymphocyte = 2.46% | |
| 74 | 9 years | M | Pallor, hepatosplenomegaly, pancytopenia | ALPS | AD | Heterozygous | FAS | NM_000043.4 | 9 | p.Arg250Gln | Missense | 26.5 | Likely Pathogenic (PM1, PM2, PM5, PP5, PP2, PP3) | Double negative T lymphocyte = 2.59% |
| 75 | 11 years | M | Hyper IgM | XL | Hemizygous | CD40LG | NM_000074.2 | 5 | p.Tyr169_Ile171del | Noframeshift Deletion | – | Likely Pathogenic (PM1, PM2, PM4, PP3) |
Expression of CD40L on activated CD69/4 + T cell: Control-95.85% Patient-1.87% |
|
| 76 | 40 years | F | Hyper IgM | XL | Hemizygous | CD40LG | NM_000074.2 | 1 | p.Lys52Lys | Synonymous | 23.1 | Likely Pathogenic (PVS1, PM2, PP3) | – | |
| 77 | 4 years | F | Eosinophilia, recurrent infections, pneumonia, skin abscess, diarrhea, stool- Giardia | Hyper IgM | XL | Homozygous | CD40 | NM_001250.5 | 4 | p.Cys103* | Nonsense | 32 | Pathogenic (PVS1, PM2, PP3) |
Class switch defect Increased B-cell: Control-52.27% Patient-88.24% Decreased switched B-cells: Control-30.68% Patient-0.39% |