Fetal anomalies
Gene: IFIH1
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene. Additional notes from clinical review: Change mode of inheritance back to monoallelic because both these conditions are AD inheritance- previous change to biallelic was most likely a misunderstanding.Created: 4 Apr 2019, 2:03 p.m.
Comment on mode of inheritance: Changed MOI back to 'monoallelic' following review by Anna de Burca (Genomics England) and Rhiannon Mellis (GOSH) in March 2019: both associated disorders (Aicardi-Goutieres syndrome 7 and 'Singleton-Merten syndrome 1) have monoallelic inheritance. The original switch to biallelic inheritance was probably due to a misunderstanding.Created: 4 Apr 2019, 12:27 p.m.
Comment on list classification: Was originally catergorised as Amber due to different DDG2P/PAGE ratings for different disorders. DDG2P rating 'Confirmed' for AICARDI-GOUTIERES SYNDROME. Changed rating from Amber to Green (with biallelic inheritance) following advice from Anna de Burca and Deirdre Cilliers that AGS is detectable in fetal setting (see reviews for details).Created: 11 Feb 2019, 12:24 p.m.
Comment on publications: PMID:25542954 describes a prenatal diagnosis of Aicardi-Goutières syndrome.Created: 11 Feb 2019, 12:16 p.m.
Comment on mode of inheritance: Changed MOI from 'monoallelic' to 'biallelic' after discussion with Genomics England clinical fellows: AD inheritance recorded on OMIM for Aicardi-Goutieres syndrome 7 and Singleton-Merten syndrome 1, however monoallelic form is associated with cardiovascular features so risk of incidental findings. Communication (via email, Feb 2019) from Deirdre Cilliers, Oxford University Hospitals, supports biallelic MOI: I would report biallelic inheritance in the known genes with an AR inheritance pattern as there is a high recurrence risk for the family, e.g. AGS caused by TREX1 and there is a clear prenatal phenotype.Created: 11 Feb 2019, 12:06 p.m.
Communication from Deirdre Cilliers, Oxford University Hospitals (via email, February 2019) to support Green rating: Yes [IFIH1 should be on the Fetal anomalies panel]. Aicardi-Goutieres is often missed in the prenatal period as it is assumed that there is congenital infection present (even if testing negative). When reading through the cases in the literature, I think that later ultrasound scans in pregnancy might have identified some of the IFIH1 mutations in addition to the more commonly found TREX1. I have had two families in the past 2 years where I suggested the diagnosis in the prenatal period, although in one family with two affected pregnancies we never found the mutations. However, the phenotype is also clear on ultrasound scan as it looks like infection and the screen for this is negative.Created: 11 Feb 2019, 11:25 a.m.
'watchlist' tag added to highlight different DD-G2P ratings for this gene.Created: 8 Nov 2018, 8:53 p.m.
In the original PAGE file: rated as Confirmed for AICARDI-GOUTIERES SYNDROME 7, and rated as Probable for SINGLETON-MERTEN SYNDROME. In the original PAGE file, MOP listed as Activating for SINGLETON-MERTEN SYNDROME, and listed as All missense/in frame for AICARDI-GOUTIERES SYNDROME 7.Created: 8 Nov 2018, 4:45 p.m.
Mode of pathogenicity
Other - please provide details in the comments
Phenotypes for gene: IFIH1 were changed from AICARDI-GOUTIERES SYNDROME 7; SINGLETON-MERTEN SYNDROME; Aicardi-Goutieres syndrome 7, 615846; Singleton-Merten syndrome 1, 182250 to Aicardi-Goutieres syndrome 7, OMIM:615846; Singleton-Merten syndrome 1, OMIM:182250
Mode of inheritance for gene: IFIH1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: ifih1 has been classified as Green List (High Evidence).
Mode of pathogenicity for gene: IFIH1 was changed from to Other
Phenotypes for gene: IFIH1 were changed from AICARDI-GOUTIERES SYNDROME 7; SINGLETON-MERTEN SYNDROME to AICARDI-GOUTIERES SYNDROME 7; SINGLETON-MERTEN SYNDROME; Aicardi-Goutieres syndrome 7, 615846; Singleton-Merten syndrome 1, 182250
Publications for gene: IFIH1 were set to
Mode of inheritance for gene: IFIH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Tag watchlist tag was added to gene: IFIH1.
Added phenotypes SINGLETON-MERTEN SYNDROME for gene: IFIH1
gene: IFIH1 was added gene: IFIH1 was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: IFIH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: IFIH1 were set to AICARDI-GOUTIERES SYNDROME 7