Skeletal dysplasiaGene: IFIH1
OI and decreasing bone density gp of SD - 3 cases with same R822Q variant. Also associated wth Aicardi-Goutieres syndrome type 7 - 615846; Review on behalf of Tracy Lester
Created: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Singleton-Merten syndrome 1 (182250)
Mode of pathogenicity
Other - please provide details in the comments
Comment on list classification: 4 cases reported. All have the same gain of function variant. Genomics England clinicians confirm the phenotype is relevant.
Created: 21 Nov 2019, 12:31 a.m. | Last Modified: 21 Nov 2019, 12:31 a.m.
Panel Version: 1.226
Comment on mode of pathogenicity: A single variant, thought to act as a gain of function, has been identified.
Created: 21 Nov 2019, 12:29 a.m. | Last Modified: 21 Nov 2019, 12:29 a.m.
Panel Version: 1.223
Associated with Singleton-Merten syndrome 1 #182250 (AD) in OMIM with short stature and various skeletal abnormalities listed as clinical features.
PMID: 25620204 - Rutsch et al 2015 - identified the same missense mutation, c.2465G>A (p.Arg822Gln), in IFIH1 in Singleton-Merten syndrome (SMS) patients from two families and a simplex case. Functional studies suggest this is a a gain-of-function IFIH1 mutation. Patients showed early and extreme aortic and valvular calcification, dental anomalies, osteopenia, and acroosteolysis .
PMID: 28319323 - Pettersson et al 2018 - identified the same mutation c.2465G>A p.(Arg822Gln), in IFIH1in a mother and daughter with Singleton-Merten syndrome. Patient 1 presented with congenital glaucoma, spastic paraplegia, severe dental anomalies, kyphosis, osteoporosis, recurrent infections, muscle weakness, aortic insufficiency, pericarditis, short stature, and SLE. Her mother presented with milder dental anomalies and finger deformities.
Created: 21 Nov 2019, 12:14 a.m. | Last Modified: 21 Nov 2019, 12:28 a.m.
Panel Version: 1.221
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: IFIH1; Initial rating suggestion: green - codon R337 only
Created: 6 Mar 2019, 11:36 a.m.
Gene: ifih1 has been classified as Green List (High Evidence).
Phenotypes for gene: IFIH1 were changed from Singleton-Merten syndrome 1 (182250) to Singleton-Merten syndrome 1, 182250
Publications for gene: IFIH1 were set to 25620204
Mode of pathogenicity for gene: IFIH1 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: IFIH1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Singleton-Merten syndrome 1 (182250) for gene: IFIH1 Publications for gene IFIH1 were changed from to 25620204
gene: IFIH1 was added gene: IFIH1 was added to Skeletal dysplasia. Sources: NHS GMS Mode of inheritance for gene: IFIH1 was set to