Table 1.
Mutations and clinical features of 51 Aicardi-Goutières syndrome (AGS) patients.
| Patient | Gene | Variant | Amino Acidic Substitution | Number of Patients (Gender) |
Annotation * | Onset ** | Clinical Score # | Clinical Phenotype | Epilepsy | GQ/IQ ° | Chilblains and/or Recurrent Fevers | Other |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | TREX1 | c.341G>A | p.R114H | 1 (Male) | Described [1] | Prenatal/neonatal | ≥12 | Spastic tetraparesis | Yes | Not evaluable | No | s- |
| P2 | TREX1 | c.262 ins AG + c.290G>A |
p.S88Kfs* + p.R97H |
1(Male) | Described [25] | Prenatal/neonatal | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | No | Antiphospholipid syndrome, thyroiditis, cerebral ischemia |
| P3 | TREX1 | c.150_151del | p.N51Gfs*50 | 1 (Male) | Described [1] | Prenatal/neonatal | ≥12 | Spastic tetraparesis | No | Not evaluable | Yes | Cardiomyopathy |
| P4 | TREX1 | c.868_885del + c.341G>A |
p.P290_A295del + p.R114H |
1(Male) | Described [1] | Prenatal/neonatal | ≥12 | Spastic-dystonic tetraparesis | Yes | Not evaluable | Yes | Cardiomyopathy, pulmonary hypertension, sensoryneural hearing loss |
| P5 | RNASEH2A | c.322C>T + c.690C>A |
p.R108W + p.F231L |
1(Female) | Described [1] | Prenatal/neonatal | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | No | Celiac disease |
| P6 | RNASEH2A | c.556C>T + c.69G>A |
p.R186W + p.V23V |
1 (Male) | Described [26] | Prenatal/neonatal | ≥12 | Spastic tetraparesis | Yes | Not evaluable | No | - |
| P7-P23 | RNASEH2B | c.529G>A | p.A177T | 17 (9 Males, 8 Females) |
Described [1,21] | Infantile to later onset | 4 patients ≤ 6 2 patients 6–12 11 patients≥ 12 |
Variable (Hemiparesis/Spastic diplegia/hypotonic-dystonic syndrome/Spastic-dystonic tetraparesis) | Yes (4 patients) No (13 patients) |
Variable (from notevaluable to 90) | Yes/No | Variable neuroradiological features (brain calcification/no calcification/diffuse microcalcification/MRI normalization at follow up) |
| P24-P30 | RNASEH2B | c.529G>A + c.488C>T |
p.A177T + p.T163I |
7 (2 Males, 5 Females) |
Described [1] | Prenatal to infantile | ≥12 | Spastic-dystonic tetraparesis | Yes (3 patients) No (4 patients) | Variable (from not evaluable to >50) | No | Variable (no other features to celiac disease) |
| P31-P32† | RNASEH2B | c.529G>A + c.218G>T |
p.A177T + p.W73L |
2 (1 Male, 1 Female) | Described [27] | Infantile | 6–12 (1 patient 11 1 patient 8) |
Spastic-dystonic tetraparesis | No | 1 patient <501 patient not evaluable | Yes | Variable neuroradiological features (brain calcification/ no calcification) |
| P33 | RNASEH2B | c.529G>A +c.Ex9_Ex11del |
p.A177T + p.Ex9_Ex11del |
1 (Male) | Novel | Prenatal/neonatal | ≥12 | Spastic-dystonic tetraparesis | Yes | Not evaluable | Yes | - |
| P34 | RNASEH2B | c.554T>G | p.V185G | 1 (Male) | Described [1] | Prenatal/neonatal | ≥12 | Spastic-dystonic tetraparesis | Yes | Not evaluable | Yes | - |
| P35 | RNASEH2B | c.529G>A + c.635C>T |
p.A177T + p.A212V |
1 (Female) | Novel | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | Yes | - |
| P36 | RNASEH2B | c.529G>A + c.64+1G>A |
p.A177T | 1 (Male) | Described [1] | Infantile | ≥12 | Spastic tetraparesis | Yes | Not evaluable | Yes | - |
| P37 | RNASEH2C | c.115G>T + c.173-1G>C |
p.D39Y | 1 (Male) | Described [1] | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | Yes | - |
| P38-P39† | SAMHD1 | c.410A>G | p.D137G | 2 (1 Male, 1 Female) | Novel | Infantile | 1patient 6 1 patient ≥12 |
Spastic paraparesis/spastic-dystonic tetraparesis | No | 1 patient 60 1 patient <50 |
Yes | - |
| P40 | SAMHD1 | c.1393C>T +c.1410+5G>C |
p.Q465* | 1 (Female) | Novel | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | <50 | Yes | - |
| P41 | SAMHD1 | Ex12_Ex16del | p.Ex12_Ex16del | 1 (Male) | Described [28] | Infantile | ≥12 | Spastic-dystonic tetraparesis | Yes | <50 | No | Cerebral vasculitis, three intracranial aneurysms |
| P42 | ADAR1 | c.577C>G + c.2608G>A |
p.P193A + p.A870T |
1 (Male) | Described [1,29] | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | No | Striatal necrosis |
| P43 | IFIH1 | c.1178A>T | p.D393V | 1 (Male) | Described [1,30] | Later onset | ≥12 | Spastic-dystonic tetraparesis | Yes | Not evaluable | No | - |
| P44 | IFIH1 | c.2471G>A | p.R824K | 1 (Male) | Described [31] | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | No | - |
| P45-46 | IFIH1 | c.2336G>A | p.R779H | 2 (2 Males) | Described [1] | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | Yes | - |
| P47 | IFIH1 | c.2159G>A | p.R720Q | 1 (Male) | Described [1] | Infantile | ≥12 | Spastic tetraparesis | Yes | Not evaluable | Yes | |
| P48 | IFIH1 | c.2561T>A | p.M854K | 1 (Male) | Novel | Later onset | <6 | Spastic paraparesis | Yes | 97 | No | Erythematous cheeks, lentiges, hyperkeratotic lesions, glaucoma, abnormal dentition, demyelinating sensory-motor polyneuropathy |
| P49 | RNASET2 | c.397_399delAAG + c.145G > T |
p.K133del +p.E49* |
1 (Male) | Described [32] | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | Not evaluable | No | Cerebellar atrophy |
| P50 | / | / | / | 1 (Male) | / | Infantile | ≥12 | Spastic-dystonic tetraparesis | No | < 50 | No | Hypopigmented lesions, thyroiditis |
| P51 | / | / | / | 1 (Female) | / | Infantile | <6 | Spastic diplegia | Yes | <50 | Yes | Hypochromic lesions on trunk |
* Novel applies to variants never described in the literature. ** Clinical onset was defined according to Livingston [5] in: Prenatal/neonatal onset, infantile onset (onset presenting in the first few months of life) and later onset (onset beyond the first year of life). # Clinical score ≥ 12 corresponds to severe disability, a score between 6 and 12 to moderate disability and a score ≤ 6 to mild disability. ° General Quotient (GQ)/Intelligence Quotient (IQ) were measured, whenever possible, using standardized tests appropriate for age (Griffiths’ Developmental Scale, Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) or WISC-R [33,34,35]. In many cases GQ/IQ was not evaluable, due to clinical severity. † Siblings.