Table 1:
Clinical characteristics of 4 individuals with AGS and PH
| Individual | 1 | 2 | 3 | 4 | |
|---|---|---|---|---|---|
| AGS | + | + | + | + | |
| Gene | IFIH1 | IFIH1 | IFIH1 | TREX1 | |
| Variant | c.1009A>G; (p.Arg337Gly) (Het., de novo) | c.2159G>A (p.Arg720Gln) (Het., de novo) | c.2936T>G (p.Leu979Trp) (Het.) | c.506G>A (p.Arg169His) (Het.) | c.581delC (p.Arg194fs) (Het.) |
| gnomAD Variant Allele Frequency | 0.0000 | 0.0000 | 0.0000 | 0.000291 | 0.0000 |
| PolyPhen Score | Probably Damaging (1.0) | Probably Damaging (0.992) | Probably Damaging (1.0) | Probably Damaging (1.0) | N/A |
| SIFT Score | Damaging | Damaging | Damaging | Damaging | N/A |
| CADD Score | 25.3 | 27.4 | 26.6 | 33 | 39 |
| ACMG Classification | Pathogenic | Likely pathogenic | Likely pathogenic | Likely pathogenic | Pathogenic |
| Age of disease presentation | 10 months | Birth | Birth | 2 months | |
| Neonatal complications | − | + | + | + | |
| Presence of PH | + | + | + | + | |
| Age of PH presentation | 16 years | 7 years | 1 month | 2 months | |
| Mechanism of diagnosis of PH | Autopsy | ECHO, cardiac catheterization | ECHO | ECHO | |
| Outcome | Death | Medical management | Death | Death | |
| Signs and symptoms of systemic inflammation | + | + | + | + | |
| CNS perivascular calcifications | + | − | + | + | |
| GI (e.g., hepatitis, poor weight gain, feeding intolerance) | + | + | + | + | |
| Dermatologic (e.g., vasculitic rashes, psoriasis, eczema) | + | + | + | − | |
| Hematologic (e.g., thrombocytopenia, anemia) | − | + | + | UK | |
| Ophthalmologic | UK | − | + | UK | |
| Hypercholesterolemia | + | − | UK | UK | |
AGS: Aicardi Goutières Syndrome; Het.: heterozygous; gnomAD: Genome Aggregation Database; CADD – Combined Annotation Dependent Deletion; ACMG – American College of Medical Genetic; N/A – Not Available; CNS: central nervous system; c/w: consistent with; GI: gastrointestinal; PH: pulmonary hypertension; UK: unknown