Interstitial Lung Disease

Gene: STAT3

Green List (high evidence)

Gain-of-function variants.
At least 3 unrelated families reported.

Created: 6 Nov 2021, 11:34 a.m. | Last Modified: 6 Nov 2021, 11:34 a.m.

Panel Version: 0.183

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
HIES (Job syndrome); Childhood bronchiectasis, interstitial lung disease or pneumatocele

Publications

• PMID: 21288777
• 18602572
• 17335882
• 25038750
• 25359994.

Mode of pathogenicity
Other

Green List (high evidence)

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. Interstitial pneumonitis reported.

STAT3 monoallelic variants were missense and in-frame deletions in both diseases.

(Hyper IgE- Loss of Function AND Autoimmune disease- Gain of function)

Created: 20 Oct 2021, 5:23 a.m. | Last Modified: 20 Oct 2021, 5:23 a.m.

Panel Version: 0.41

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

• 17881745
• 14566054
• 25349174
• 25038750
• 25359994