Autoinflammatory Disorders
Gene: IFIH1
Classified as DEFINITIVE by Leukodystrophy and Leukoencephalopathy ClinGen GCEP on 23/08/2024 - https://search.clinicalgenome.org/CCID:008354
GoF is the mechanism of disease.Created: 16 Sep 2024, 3:51 a.m. | Last Modified: 16 Sep 2024, 3:51 a.m.
Panel Version: 1.2013
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
IFIH1-related type 1 interferonopathy MONDO:0700262
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
IFIH1 encodes MDA5, a key cystolic sensor for viral nucleic acids. Rare, likely loss-of-functions IFIH1 variants identified in eight independent probands with Very Early Onset Inflammatory Bowel Disease (VEOIBD) from a combined cohort of 42 children. IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p=0.007).
In one case of neonatal-onset IBD, a homozygous truncating variant was identified. There were seven carriers of LoF variants identified (range of onset 6 months to 6 years of age). In three of these cases, a second hypomorphic missense variant was identified.
Luciferase reporter assays were employed to assess MDA5 activity. In some cases, the second missense variant was either proven to not affect protein function or was in cis with the LoF variant.
Complete and partial MDA5 deficiency is associated with VEOIBD with variable penetrance and expressivity, suggesting a role for impaired intestinal viral sensing in IBD pathogenesis.Created: 6 Sep 2021, 6:04 a.m. | Last Modified: 6 Sep 2021, 6:17 a.m.
Panel Version: 0.9088
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes
Inflammatory Bowel Disease
Publications
Gain of function variants.
Sources: Expert listCreated: 5 Apr 2020, 9:12 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Aicardi-Goutieres syndrome 7, MIM# 615846
Gene: ifih1 has been classified as Green List (High Evidence).
Gene: ifih1 has been classified as Red List (Low Evidence).
gene: IFIH1 was added gene: IFIH1 was added to Systemic Autoinflammatory Disease_Periodic Fever. Sources: Expert list Mode of inheritance for gene: IFIH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: IFIH1 were set to Aicardi-Goutieres syndrome 7, MIM# 615846 Review for gene: IFIH1 was set to GREEN