Table 1. IEI with described ILC... | Rockefeller University Press

Table 1.

IEI with described ILC abnormalities: Clinical characteristics

Disease	Gene	Inheritance	OMIM	IUIS tables major category; subcategory	Microbial susceptibility	Immune dysregulation
gc deficiency SCID	IL2RG	XL	308380	T1; ST1	Recurrent severe viral, bacterial, and fungal infections; diarrhea	Treg defects; hypomorphic mutations in IL-2Rγ result in CID with immune dysregulation
JAK3 deficiency SCID	JAK3	AR	600173	T1; ST1	Recurrent or severe respiratory infections; oral thrush (candidiasis); pneumonia	Treg defects
IL7Ra deficiency SCID	IL7R	AR	146661	T1; ST1	Recurrent severe viral, bacterial, and fungal infections; candidiasis; chronic diarrhea; Pneumocystis jirovecii pneumonia	Treg defects; may present with immune dysregulation; chronic inflammatory diseases
RAG1 deficiency SCID	RAG1	AR	179615	T1; ST2	Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection	Hypomorphic mutations associated with immune dysregulation
RAG2 deficiency SCID	RAG2	AR	179616	T1; ST2	Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection	Hypomorphic mutations associated with immune dysregulation
RORgt deficiency	RORC	AR	616622	T6; ST1	Mycobacteria and Candida albicans	No broad infectious or autoimmune phenotype
IL-12Rb2 deficiency	IL12RB2	AR	601642	T6; ST1	Mycobacteria and Salmonella	Deficiency is associated with autoimmunity in mice; human data are scarce
IL-23R deficiency	IL23R	AR	607562	T6; ST1	Mycobacteria and Salmonella	SNPs associated with autoimmunity, not null or LOF
IL-12R and IL-23Rb1 deficiency	IL12RB1	AR	601604	T6; ST1	Mycobacteria and Salmonella	Only 3 out of 300 LOF showed autoimmunity; SNPs associated with autoimmunity
LAD1	ITGB2	AR	600065	T5; ST2	Recurrent bacterial and fungal infections	Leukocytosis
DOCK8 deficiency (HIES)	DOCK8	AR	243700	T1; ST3	Recurrent cutaneous viral, fungal, and staphylococcal infections	Treg defects; low NK cells with poor function; eosinophilia; severe atopy; cancer diathesis
WAS LOF	WAS	XL	300392	T2; ST1	Recurrent viral and bacterial infections	Thrombocytopenia with small platelets; eczema; lymphoma; autoimmune disease; IgA nephropathy; vasculitis; XL thrombocytopenia is a mild form of WAS—bloody diarrhea; Treg defects
ITK deficiency	ITK	AR	186973	T1; ST3	Epstein–Barr virus (EBV)	EBV-associated B cell lymphoproliferation; lymphoma
BCL11B deficiency	BCL11B	AD	617237	T2; ST9	Upper respiratory infections	Immunological dysregulation expressed as allergy, asthma, eczema, eosinophilia, and severe atopy
DIAPH1 deficiency	DIAPH1	AR	602121	T2; ST9	Recurrent viral and bacterial infections	B lymphoma; decreased T cell activation/proliferation in vitro; impaired adhesion/microtubule organizing center (MTOC repositioning to immune synapse; defective cytoskeletal organization; mitochondrial dysfunction in SCBMS pathogenesis
STAT3 LOF (HIES)	STAT3 (LOF, DN)	AD	102582	T2; ST5	Bacterial infections—boils and pulmonary abscesses, pneumatoceles due to Staphylococcusaureus; Pulmonary aspergillus; Pneumocystis jirovecii; mucocutaneous candidiasis	Eczema
BTK deficiency (XLA)	BTK	XL	300300	T3; ST1	Severe bacterial infections	Normal numbers of pro-B cells
CVID, no gene defect specified	Unknown	Variable	607594 616576 615577 240500 614700 604558	T3; ST2	Recurrent infections	Some show polyclonal lymphoproliferation, autoimmune cytopenias, and/or granulomatous disease

Disease	Gene	Inheritance	OMIM	IUIS tables major category; subcategory	Microbial susceptibility	Immune dysregulation
gc deficiency SCID	IL2RG	XL	308380	T1; ST1	Recurrent severe viral, bacterial, and fungal infections; diarrhea	Treg defects; hypomorphic mutations in IL-2Rγ result in CID with immune dysregulation
JAK3 deficiency SCID	JAK3	AR	600173	T1; ST1	Recurrent or severe respiratory infections; oral thrush (candidiasis); pneumonia	Treg defects
IL7Ra deficiency SCID	IL7R	AR	146661	T1; ST1	Recurrent severe viral, bacterial, and fungal infections; candidiasis; chronic diarrhea; Pneumocystis jirovecii pneumonia	Treg defects; may present with immune dysregulation; chronic inflammatory diseases
RAG1 deficiency SCID	RAG1	AR	179615	T1; ST2	Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection	Hypomorphic mutations associated with immune dysregulation
RAG2 deficiency SCID	RAG2	AR	179616	T1; ST2	Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection	Hypomorphic mutations associated with immune dysregulation
RORgt deficiency	RORC	AR	616622	T6; ST1	Mycobacteria and Candida albicans	No broad infectious or autoimmune phenotype
IL-12Rb2 deficiency	IL12RB2	AR	601642	T6; ST1	Mycobacteria and Salmonella	Deficiency is associated with autoimmunity in mice; human data are scarce
IL-23R deficiency	IL23R	AR	607562	T6; ST1	Mycobacteria and Salmonella	SNPs associated with autoimmunity, not null or LOF
IL-12R and IL-23Rb1 deficiency	IL12RB1	AR	601604	T6; ST1	Mycobacteria and Salmonella	Only 3 out of 300 LOF showed autoimmunity; SNPs associated with autoimmunity
LAD1	ITGB2	AR	600065	T5; ST2	Recurrent bacterial and fungal infections	Leukocytosis
DOCK8 deficiency (HIES)	DOCK8	AR	243700	T1; ST3	Recurrent cutaneous viral, fungal, and staphylococcal infections	Treg defects; low NK cells with poor function; eosinophilia; severe atopy; cancer diathesis
WAS LOF	WAS	XL	300392	T2; ST1	Recurrent viral and bacterial infections	Thrombocytopenia with small platelets; eczema; lymphoma; autoimmune disease; IgA nephropathy; vasculitis; XL thrombocytopenia is a mild form of WAS—bloody diarrhea; Treg defects
ITK deficiency	ITK	AR	186973	T1; ST3	Epstein–Barr virus (EBV)	EBV-associated B cell lymphoproliferation; lymphoma
BCL11B deficiency	BCL11B	AD	617237	T2; ST9	Upper respiratory infections	Immunological dysregulation expressed as allergy, asthma, eczema, eosinophilia, and severe atopy
DIAPH1 deficiency	DIAPH1	AR	602121	T2; ST9	Recurrent viral and bacterial infections	B lymphoma; decreased T cell activation/proliferation in vitro; impaired adhesion/microtubule organizing center (MTOC repositioning to immune synapse; defective cytoskeletal organization; mitochondrial dysfunction in SCBMS pathogenesis
STAT3 LOF (HIES)	STAT3 (LOF, DN)	AD	102582	T2; ST5	Bacterial infections—boils and pulmonary abscesses, pneumatoceles due to Staphylococcusaureus; Pulmonary aspergillus; Pneumocystis jirovecii; mucocutaneous candidiasis	Eczema
BTK deficiency (XLA)	BTK	XL	300300	T3; ST1	Severe bacterial infections	Normal numbers of pro-B cells
CVID, no gene defect specified	Unknown	Variable	607594 616576 615577 240500 614700 604558	T3; ST2	Recurrent infections	Some show polyclonal lymphoproliferation, autoimmune cytopenias, and/or granulomatous disease

XL, X-linked; AD, autosomal dominant; AR, autosomal recessive; T, table; ST, sub-table; SCBMS, seizures, cortical blindness, microcephaly syndrome.