Genetic and clinical features of IFIH1 variants previously reported in epilepsy
| Variants | gnomAD | Sex | Inheritance | Location | Diagnosis | Seizure | Other manifestations | Brain imaging | Reference | ||
| V.4.1.0 | V.2.1.1 | ||||||||||
| Missense variants | c.1178A>T/p.Asp393Val | – | – | M | De novo | Hel1 | Neuroregression | Seizures | Fever and rash, severe spastic tetraparesis, axial hypotonia and a loss of speech, and a rapid loss of motor and intellectual skills | Basal ganglia calcification | Rice et al 25 |
| c.1354G>A/p.Ala452Thr | – | – | M | De novo | Hel1 | AGS7 | EFS+ | Hypertonia, spastic quadriplegia and microcephaly | Brain atrophy, bilateral in the basal ganglia and white matter calcification | Oda et al 12 | |
| c.2159G>A/p.Arg720Gln | 6.841×10−7 | – | M | De novo | Hel2 | AGS7 | Intractable epilepsy (died of pneumonia at the age of 2 years) | Irritable and fed poorly, spastic-dystonic tetraparesis, intrauterine growth retardation and microcephaly | Cerebral atrophy with calcifications and white matter disease | Rice et al 25 | |
| c.2317G>C/p.Arg773Gln | – | – | M | De novo | Hel2 | Cerebral palsy | EE | Spastic diplegia, intelligence disturbance and neurodevelopmental delay | Calcification | Rosello et al 31 | |
| c.2336G>A/p.Arg779His | 1.374×10−6 | 4.011×10−6 | F | De novo | Hel2 | AGS7 | EFS+ | Dystonia, hypotonia, spastic quadriplegia and progressive microcephaly | Brain atrophy, bilateral basal ganglia and subcortical calcification | Oda et al 12 | |
| c.2486C>G/p.Thr829Ser | – | – | M | NA | Hel2 | AGS7 | Seizures | Spastic diplegia and rapid neurological decline | Abnormal white matter and calcification | Rice et al 29 | |
| c.2561T>A/p.Met854Lys | – | – | F | De novo | Pincer | AGS7 and SGMRT1 | EFS+ (febrile seizures every year) | Moderate motor and mental retardation | Bilateral calcification of the deep frontal lobes and the globus pallida | Takeichi et al 42 | |
| Truncation variants | c.1852C>T/p.Arg618Ter | 1.426×10−5 | 1.992×10−5 | F | De novo | Hel2i | AGS7 | Seizures (deceased) | Microcephaly, muscular hypotonia and global developmental delay | NA | Liu et al 7 |
| c.2020_c.2023delAGAT/ p.Arg674PhefsTer3 | – | – | NA | NA | Hel2i | Early onset epileptic encephalopathy | Frequent focal seizures (severely) | Severe developmental delay | A wide range of symmetrical abnormalities in the white matter | Ma et al 28 | |
| c.2665A>T/p.Lys889Ter | 1.369×10−6 | 3.989×10−6 | F | Homozygous (paternal and maternal) | Pincer | 3-phosphoglycerate dehydrogenase deficiency | EE (occurring once or twice per day with mild myoclonia) | Fever and respiratory infections, microcephaly, severe psychomotor retardation | Simplified gyral pattern, hypoplastic corpus callosum | Zaki et al 32 | |
AGS7, Aicardi-Goutières syndrome 7; EE, epileptic encephalopathy; EFS+, epilepsy with febrile seizures plus; F, female; gnomAD, Genome Aggregation Database; GTCS, generalised tonic-clonic seizure; Hel, helicase domain; M, male; NA, not available; SGMRT1, Singleton-Merten syndrome 1.