Table 1.
Clinical characteristics and variants of 25 PID patients
| ID | Gender | Gene | Variants [RefSeq ID] | In silico prediction (SIFT/PolyPhen) | Disease [OMIM#] | Inheritance/zygosity | Associated features | IUIS classification | 180 days of age outcome |
|---|---|---|---|---|---|---|---|---|---|
| 1 | M | JAK3 |
c.3050T>C(p.Leu1017Pro) c.1744C>T(p.Arg582Trp) |
Deleterious/probably damaging Deleterious/possibly damaging |
JAK3 deficiency [OMIM: 600173] |
AR/compound het | Life‐threatening infections; atopic dermatitis; thrombocytopenia; anaemia | Immunodeficiencies affecting cellular and humoral immunity/T‐B + SCID | ID at 15 weeks, 6 days |
| 12 | F | IL10RA |
c.301C>T(p.Arg101Trp) c.1283delC(p.Pro428Argfs*20) |
Deleterious/probably damaging ‐/‐ |
IL‐10Ra deficiency [OMIM: 146933] |
AR/compound het | Life‐threatening infections; intractable diarrhoea; thrombocytopenia; anaemia | Diseases of immune dysregulation/immune dysregulation with colitis | NND at 26 days |
| 13 | M | IL10RA |
c.301C>T(p.Arg101Trp) c.537G>A(p.=) |
Deleterious/probably damaging ‐/‐ |
IL‐10Ra deficiency [OMIM: 146933] |
AR/compound het | Recurrent infections; intractable diarrhoea; atopic dermatitis; failure to thrive secondary to recurrent infections or intractable diarrhoea | Diseases of immune dysregulation/immune dysregulation with colitis | Survival |
| 14 | M | IL10RA |
c.106G>A(p.Ala36Thr) c.299T>G(p.Val100Gly) |
Deleterious/probably damaging Deleterious/probably damaging |
IL‐10Ra deficiency [OMIM: 146933] |
AR/compound het | Recurrent infections; intractable diarrhoea; atopic dermatitis; failure to thrive secondary to recurrent infections or protracted diarrhoea (cytomegalovirus infection) | Diseases of immune dysregulation/immune dysregulation with colitis | Survival |
| 15 | M | IL2RG |
c.421C>T(p.Gln141*) |
‐ | γc deficiency (common gamma chain SCID, CD132 deficiency) [OMIM: 308380] | XL/inherited hemi | Life‐threatening infections; atopic dermatitis; thrombocytopenia; anaemia | Immunodeficiencies affecting cellular and humoral immunity/T‐B + SCID | ID at 20 weeks |
| 16 | M | CXCR4 |
c.685T>A(p.Ser229Thr) |
Tolerated/possibly damaging | WHIM (warts, hypogammaglobulinaemia, infections, myelokathexis) syndrome [OMIM: 162643] | AD/inherited het (inherited from mildly affected mother) | Recurrent infections; failure to thrive secondary to recurrent infections; thrombocytopenia; neutropenia; hepatosplenomegaly. | Defects in intrinsic and innate immunity/epidermodysplasia verruciformis (HPV) | Survival |
| 17 | M | ITGB2 |
c.817G>A(p.Gly273Arg) |
Deleterious/possibly damaging | Leucocyte adhesion deficiency type 1 (LAD1) [OMIM: 600065] | AR/homozygous | Life‐threatening infections; recurrent infections; delayed cord separation; atopic dermatitis; failure to thrive secondary to recurrent infections; anaemia; leucocytosis | Congenital defects of phagocyte number or function/defects of motility | Survival |
| 28 | M | 22q11.2 del | chr22q11.2 del | ‐ | Chromosome 22q11.2 deletion syndrome (22q11.2DS) [OMIM: 602054] | AD/het (biological parents unavailable) | Life‐threatening infections (blood culture: Klebsiella pneumonia); abnormal faeces; congenital heart defects | Combined immunodeficiencies with associated or syndromic features/thymic defects with additional congenital anomalies | Survival |
| 39 | M | IKBKG |
c.1110delinsTT(p.Ala371Cysfs*24) |
‐ | EDA‐ID because of IKBKG deficiency [OMIM: 300248] | XL/inherited hemi | Life‐threatening infections; recurrent infections; failure to thrive secondary to recurrent infections; thrombocytopenia. (blood culture: Klebsiella pneumonia) | Combined immunodeficiencies with associated or syndromic features/anhidrotic EDA‐ID | ID at 8 weeks, 4 days |
| 41 | F | IKBKG |
Exon 4‐10 del |
‐ | EDA‐ID because of IKBKG deficiency [OMIM: 300248] | XL/inherited het | Atopic dermatitis | Combined immunodeficiencies with associated or syndromic features/anhidrotic EDA‐ID | Survival |
| 46 | F | SPINK5 |
c.377_378del(p.Tyr126*) c.2468dup(p.Lys824Glufs*4) |
‐ ‐ |
Comel‐Netherton syndrome [OMIM: 605010] | AR/compound het | Life‐threatening infections; atopic dermatitis; anaemia | Combined immunodeficiencies with associated or syndromic features/hyper‐IgE syndromes (HIES) | ID at 5 weeks, 5 days |
| 47 | F | IKBKG |
Exon 4‐10 del |
‐ | EDA‐ID because of IKBKG deficiency [OMIM: 300248] | XL/Inherited het | Atopic dermatitis | Combined immunodeficiencies with associated or syndromic features/anhidrotic EDA‐ID | Survival |
| 48 | M | CHD7 |
c.6292C>T(p.Arg2098*) |
‐ | CHARGE syndrome because of CHD7 deficiency [OMIM: 608892] | AD/de novo het | Recurrent infections; anaemia; heart anomaly; choanal atresia; genital and ear anomalies | Combined immunodeficiencies with associated or syndromic features/thymic defects with additional congenital anomalies | Survival |
| 52 | M | KMT2D |
c.14382G>A(p.=) |
‐ | Kabuki syndrome 1 because of KMT2D deficiency [OMIM: 602113] | AD/de novo het | Life‐threatening infections; protracted diarrhoea; abnormal faeces; congenital heart defects | Combined immunodeficiencies with associated or syndromic features/other defects | Survival |
| 61 | F | IL10RA |
c.251C>T(p.Thr84Ile) c.537G>A(p.=) |
Deleterious/probably damaging ‐ |
IL‐10Ra deficiency [OMIM: 146933] | AR/compound het | Life‐threatening infections; recurrent infections; intractable diarrhoea; failure to thrive secondary to recurrent infections or protracted diarrhoea; thrombocytopenia; anaemia | Diseases of immune dysregulation/immune dysregulation with colitis | Survival |
| 63 | M | UNC13D |
c.766C>T(p.Arg256*) c.640C>T(p.Arg214*) |
‐ ‐ |
UNC13D/Munc13‐4 deficiency (FHL3) [OMIM: 608897] | AR/compound het | Life‐threatening infections; neutropenia; thrombocytopenia | Diseases of immune dysregulation/familial haemophagocytic lymphohistiocytosis (FHL syndromes) | ID at 23 weeks, 6 days |
| 64 | M | IKBKG |
c.662T>C(p.Leu221Pro) |
Deleterious/probably damaging |
EDA‐ID because of IKBKG deficiency [OMIM: 300248] | XL/inherited hemi | Life‐threatening infections; recurrent infections; atopic dermatitis; anaemia; (blood culture: Acinetobacter baumannii) | Combined immunodeficiencies with associated or syndromic features/anhidrotic EDA‐ID | ID at 19 weeks, 4 days |
| 65 | M | IKBKG |
Exon 4‐10 del |
‐ | EDA‐ID because of IKBKG deficiency [OMIM: 300248] |
XL/het (mosaic mother) |
Atopic dermatitis | Combined immunodeficiencies with associated or syndromic features/anhidrotic EDA‐ID | Survival |
| 66 | F | KMT2D |
c.11017del(p.Asn3674Ilefs*75) |
‐ | Kabuki syndrome 1 because of KMT2D deficiency [OMIM: 602113] | AD/de novo het | Recurrent infections; anaemia; facial abnormalities; congenital heart defects | Combined immunodeficiencies with associated or syndromic features/other defects | Survival |
| 67 | F | IKBKG |
Exon 4‐10 del |
‐ | EDA‐ID because of IKBKG deficiency [OMIM: 300248] | XL/inherited het | Atopic dermatitis | Combined immunodeficiencies with associated or syndromic features/anhidrotic EDA‐ID | Survival |
| 68 | M | POLE |
c.1181_1182del(p.Gln394Argfs*29) c.3587C>T(p.Thr1196Met) |
‐ Tolerated/benign |
POLE1 (polymerase ε subunit 1) deficiency (FILS syndrome) [OMIM: 174762] | AR/compound het | Life‐threatening infections; anaemia; facial dysmorphism (cytomegalovirus infection) | Combined immunodeficiencies with associated or syndromic features/DNA repair defects other than those listed in immunodeficiencies affecting cellular and humoral immunity | Survival |
| 69 | M | CYBB |
c.1151 + 1G>A(p.?) |
‐ | X‐linked chronic granulomatous disease (CGD), gp91phox [OMIM: 300481] | XL/inherited hemi | Life‐threatening infections; atopic dermatitis | Congenital defects of phagocyte number or function/defects of respiratory burst | ID at 24 weeks, 4 days |
| 70 | F | KMT2D |
c.10595T>C(p.Ile3532Thr) |
Deleterious/probably damaging |
Kabuki syndrome 1 because of KMT2D deficiency [OMIM: 602113] | AD/de novo het | Life‐threatening infections; facial abnormalities; congenital heart defects | Combined immunodeficiencies with associated or syndromic features/other defects | Survival |
| 71 | M | KMT2D |
c.1967del(p.Leu656Argfs*274) |
‐ | Kabuki syndrome 1 because of KMT2D deficiency [OMIM: 602113] | AD/de novo het | Life‐threatening infections; facial abnormalities; congenital heart defects | Combined immunodeficiencies with associated or syndromic features/other defects | Survival |
| 72 | F | CHD7 |
c.6157C>T(p.Arg2053*) |
‐ | CHARGE syndrome because of CHD7 deficiency [OMIM: 608892] | AD/de novo het | Intractable diarrhoea; heart anomaly; choanal atresia; genital and ear anomalies | Combined immunodeficiencies with associated or syndromic features/thymic defects with additional congenital anomalies | Survival |
AD, autosomal dominant inheritance; AR, autosomal recessive inheritance; EDA‐ID, epidermodysplasia immunodeficiency; F, female; hemi, hemizygous; het, heterozygous; hom, homozygous; ID, infant death; IUIS, International Union of Immunological Societies; M, male; NND, neonatal death; SCID, severe combined immune deficiency; XL, X‐linked inheritance.