Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: IL6STPMID: 33517393 - Materna-Kiryluk et al 2021 - describe a patient with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphic features. The patient was found using exome sequencing to have a de novo IL6ST Tyr186_Tyr190del variant, which was present as a mosaic. It was found in around 15–40% of cells depending on the tissue (blood, urine sediment, hair bulbs and buccal swab).Created: 4 May 2021, 6:26 p.m. | Last Modified: 4 May 2021, 6:26 p.m.
Panel Version: 2.419
Publications
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 4 Mar 2022, 10:17 a.m. | Last Modified: 4 Mar 2022, 10:17 a.m.
Panel Version: 2.529
Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).Created: 20 Oct 2020, 3:05 p.m. | Last Modified: 20 Oct 2020, 3:05 p.m.
Panel Version: 2.342
Comment on list classification: Based on expert review and the reporting of additional variants.Created: 5 May 2020, 4:07 p.m. | Last Modified: 5 May 2020, 4:07 p.m.
Panel Version: 2.158
Comment on phenotypes: Eosinophilia;Eczema;Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis;Abnormal acute-phase responses;Recurrent infections;Elevated IgE;Combined immunodeficiencies with associated or syndromic featuresCreated: 5 May 2020, 4:03 p.m. | Last Modified: 5 May 2020, 4:03 p.m.
Panel Version: 2.157
Also known as gp130. Two families with bi-allelic missense variants and immunological phenotype described initially. More recently, five individuals from three families reported with a more complex Stuve-Wiedemann-like phenotype reported, including skeletal dysplasia and neonatal lung dysfunction with additional features such as congenital thrombocytopenia, eczematoid dermatitis, renal abnormalities, and defective acute-phase response. These three families had bi-allelic LoF variants (nonsense and canonical splice site). Several mouse models support gene-disease association.
2020: 12 individuals from 8 unrelated families with seven different mono-allelic truncating variants, dominant negative effect proposed.Created: 10 Apr 2020, 8:20 a.m. | Last Modified: 10 Apr 2020, 8:20 a.m.
Panel Version: 2.51
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Hyper-IgE recurrent infection syndrome 4, autosomal recessive, MIM# 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.; Hyper-IgE syndrome, autosomal dominant
Publications
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
Comment on list classification: New gene added for reviewCreated: 26 Feb 2020, 4:30 p.m. | Last Modified: 26 Feb 2020, 4:30 p.m.
Panel Version: 2.5
New gene suggested by expert reviewer- unable to do a full curational review (Green rating recommended) as we are waiting for new PanelApp features before this gene can be added to this GMS panel.Created: 22 Jan 2020, 11:36 a.m. | Last Modified: 22 Jan 2020, 11:36 a.m.
Panel Version: 2.0
Publications
At least two unrelated cases with homozygous loss-of-function variants and compelling functional support.Created: 18 Jan 2020, 7:44 a.m. | Last Modified: 18 Jan 2020, 7:44 a.m.
Panel Version: 2.0
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hyper-IgE syndrome
Publications
Tag for-review was removed from gene: IL6ST.
Source Expert Review Green was added to IL6ST. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: il6st has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: IL6ST.
Gene: il6st has been classified as Green List (High Evidence).
Phenotypes for gene: IL6ST were changed from Eosinophilia; Eczema; Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis; Abnormal acute-phase responses; Recurrent infections; Elevated IgE; Combined immunodeficiencies with associated or syndromic features to Hyper-IgE recurrent infection syndrome 4, autosomal recessive 618523; Stuve-Wiedemann-like syndrome: skeletal dysplasia, neonatal lung dysfunction, thrombocytopenia, dermatitis, defective acute-phase response.; Hyper-IgE syndrome, autosomal dominant
Publications for gene: IL6ST were set to 31235509; 32086639; 30309848; 28747427; 32048120
Publications for gene IL6ST were updated from 32048120; 31235509; 32086639 to 31235509; 32086639; 30309848; 28747427; 32048120
Source IUIS Classification December 2019 was added to IL6ST. Added phenotypes Bacterial infections, boiles, eczema, pulmonary abscesses, pneumatoceles, bone fractures, scoliosis, retention of primary teeth, craniosynostosis; Combined immunodeficiencies with associated or syndromic features for gene: IL6ST Publications for gene IL6ST were updated from 31235509 to 32048120; 31235509; 32086639
Gene: il6st has been classified as Red List (Low Evidence).
gene: IL6ST was added gene: IL6ST was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: IL6ST was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IL6ST were set to 31235509 Phenotypes for gene: IL6ST were set to Recurrent infections; Abnormal acute-phase responses; Elevated IgE; Eczema; Eosinophilia Review for gene: IL6ST was set to GREEN