Disorders of immune dysregulation
Gene: STAT3
Well-established disease-gene association for hyper-IgE syndrome; identified heterozygous STAT3 variants in over 50 familial and sporadic cases; dominant-negative loss of function; multiple mouse models Hyper IgE individuals presented with the triad of staphylococcal abscesses, pneumonia with pneumatocele formation, and extremely elevated IgE.
15 unrelated families with Autoimmune disease, multisystem, infantile-onset, 1; 13 STAT3 variants identified (5 were de novo); gain of function; multiple mouse models Autoimmune disease, multisystem, infantile-onset, 1 individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature. STAT3 monoallelic variants were missense and in-frame deletions in both diseases.
(Hyper IgE- Loss of Function AND Autoimmune disease- Gain of function)Created: 12 Aug 2021, 8:28 a.m. | Last Modified: 12 Aug 2021, 8:28 a.m.
Panel Version: 0.8776
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Hyper-IgE recurrent infection syndrome MIM# 147060; Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952
Publications
18 individuals from 15 unrelated families; Multiple mouse models
All 13 heterozygous variants reported have been missense or in-frame deletions that result in a gain of function; 5 of these de novo
Individuals exhibited various clinical features, with most presenting with lymphadenopathy, autoimmune cytopaenias, multiorgan autoimmunity, infections, and short stature.Created: 12 Aug 2021, 6:28 a.m. | Last Modified: 12 Aug 2021, 6:28 a.m.
Panel Version: 0.92
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Lymphoproliferation; solid organ autoimmunity; recurrent infections; short stature; eczema; delayed puberty; dental abnormalities; autoimmune interstitial lung disease; juvenile-onset arthritis; primary hypothyroidism
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: stat3 has been classified as Green List (High Evidence).
Phenotypes for gene: STAT3 were changed from to Autoimmune disease, multisystem, infantile-onset, 1 MIM# 615952; Lymphoproliferation; solid organ autoimmunity; recurrent infections; short stature; eczema; delayed puberty; dental abnormalities; autoimmune interstitial lung disease; juvenile-onset arthritis; primary hypothyroidism
Publications for gene: STAT3 were set to
Mode of pathogenicity for gene: STAT3 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for gene: STAT3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
gene: STAT3 was added gene: STAT3 was added to Disorders of immune dysregulation_MGHA_AGHA_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Immunology Flagship Mode of inheritance for gene: STAT3 was set to Unknown