TABLE 2.
Molecular and clinical data by family
| Family | Individual | Sex | cDNA | Protein | Inheritance (number of mutation-positive individuals) |
Previously reported (reference) |
Clinical phenotype | Status at last contact (age in years) |
|---|---|---|---|---|---|---|---|---|
| AGS102 | P1 | M | c.2159G>A | p.Arg720Gln | De novo | Rice et al. (2014) | AGS | Deceased (2) |
| AGS163 | P1 | M | c.2336G>A | p.Arg779His | De novo | Rice et al. (2014) | AGS | Alive (13) |
| AGS237 (LD_0762) | P1 | M | c.1009A>G | p.Arg337Gly | De novo | Rice et al. 2014; Adang et al., 2018 | Neuroregression and SD starting at age 15 months | Deceased (16) |
| AGS259 | P1 | M | c.2336G>A | p.Arg779His | Familial (3) | Rice et al. (2014) | AGS | Alive (13) |
| P2 (father of P1) | M | Clinically nonpenetrant | Alive (54) | |||||
| P3 (mother of P2) | F | Clinically nonpenetrant | Deceased (84) | |||||
| AGS376 | P1 | M | c.2335C>T | p.Arg779Cys | No parental testing | Rice et al. (2014) | AGS with LLD | Deceased (3) |
| AGS524 | P1 | F | c.1483G>A | p.Gly495Arg | Familial (2)(shown to have occurred de novo in P2) | Rice et al. (2014); Hacohen et al. 2015; Crow et al. 2015; McLellan et al. 2018 | SP with LLD and AQP4 + TM | Alive (10) |
| P2 (father of P1) | M | Pure SP | Alive (39) | |||||
| AGS531 | P1 | F | c.2544T>G | p.Asp848Glu | Familial (5) | Ruaud et al. (2018) | SP with ICC | Alive (13) |
| P2 (brother of P1) | M | Clinically nonpenetrant | Alive (13) | |||||
| P3 (father of P1 and P2) | M | SP with ICC | Alive (40) | |||||
| P4 (brother of P3) | M | SP with ICC | Alive (38) | |||||
| P5 (father of P3 and P4) | M | Clinically non-penetrant | Alive (66) | |||||
| AGS626 | P1 | M | c.1178A>T | p.Asp393Val | De novo | Rice et al. (2014) | Neuroregression and SD starting at 13 months | Alive (13) |
| AGS647 | P1 | M | c.2159G>A | p.Arg720Gln | De novo | Rice et al. (2014) | AGS | Alive (2) |
| AGS674 | P1 | M | c.992C>G | p.Thr331Arg | De novo | Unreported | SP-SMS overlap | Alive (14) |
| AGS723 | P1 | F | c.2335C>T | p.Arg779Cys | Mother negative; no paternal DNA | Unreported | SP with ICC | Alive (19) |
| AGS735 | P1 | M | c.2471G>A | p.Arg824Lys | De novo | Galli et al. 2018 | Neuroregression and SD starting at 12 months | Alive (19) |
| AGS755 | P1 | M | c.1465G>A | p.Ala489Thr | Familial (3) | Bursztejn et al. (2015) | CLL | Alive (4) |
| P2 (brother of P1) | M | AGS-SMS overlap | Alive (3) | |||||
| P3 (father of P1 and P2) | M | SMS-like | Alive (41) | |||||
| AGS848 | P1 | M | c.1165G>A | p.Gly389Arg | Familial (3) | Unreported | AGS | Alive (8) |
| P2 (father of P1) | M | SP | Alive (42) | |||||
| P3 (maternal grandmother of P2) | F | Clinically nonpenetrant | Alive (84) | |||||
| AGS1001 | P1 | M | c.1347C>G | p.Asn449Lys | De novo | Unreported | SP | Alive (19) |
| AGS1004 | P1 | F | c.2335C>T | p.Arg779Cys | De novo | Unreported | AGS (neuroregression with onset at age 8 months) | Alive (8) |
| AGS1156 | P1 | M | c.2335C>T | p.Arg779Cys | De novo | Kothur et al. 2018 | AGS (neuroregression with onset at age 8 months) | Alive (5) |
| AGS1290 | P1 | M | c.2486C>G | p.Thr829Ser | 2 affected (no parental DNA) | Unreported | AGS | Alive (6) |
| P2 (brother of P1) | M | AGS | Alive (4) | |||||
| AGS1351 | P1 | F | c.2336G>A | p.Arg779His | De novo | Unreported | AGS | Deceased (2) |
| AGS1430 | P1 | M | c.2866A>G | p.Ile956Val | Familial (3) | Unreported | SP with ICC with onset at age 6 years | Alive (14) |
| P2 (father of P1) | M | SP with onset at age 2 years | Alive (50) | |||||
| P3 (father of P2) | M | Clinically non-penetrant | Alive (72) | |||||
| AGS1504 (LD_1175) | P1 | F | c.2159G>A | p.Arg720Gln | De novo | Unreported | AGS | Alive (10) |
| AGS1509 | P1 | M | c.2336G>A | p.Arg779His | De novo | Unreported | AGS | Alive (8) |
| AGS1514 | P1 | M | c.2465G>A | p.Arg822Gln | De novo | Buers et al. (2017) | SD with ICC | Alive (6) |
| AGS1938 | P1 | F | c.992C>T | p.Thr331Ile | Familial (3) | de Carvalho et al. (2017) | SMS | Alive (18) |
| P2 (mother of P1) | F | SMS | Alive (45) | |||||
| P3 (sister of P2) | F | SMS | Alive (27) | |||||
| AGS1972 | P1 | F | c.992C>G | p.Thr331Arg | Familial (2) | de Carvalho et al. (2017) | SMS | Alive (9) |
| P2 (father of P1) | M | SMS | Alive (47) | |||||
| AGS2081 | P1 | M | c.2561T>A | p.Met854Lys | De novo | Unreported | SP-SMS overlap | Alive (12) |
| AGS2154 (LD_1240) | P1 | M | c.2335C>T | p.Arg779Cys | Familial (2) | Unreported | Unilateral white matter disease with normal development | Alive (13) |
| P2 (mother of P1) | F | Clinically nonpenetrant | Alive (40) | |||||
| AGS2177 | P1 | M | c.2336G>A | p.Arg779His | Familial (3) | Neuroregression and SD starting at age 12 months | Alive (29) | |
| P2 (mother of P1) | F | Clinically nonpenetrant | Alive (62) | |||||
| P3 (sister of P1) | F | Clinically nonpenetrant | Alive (33) | |||||
| AGS2180 | P1 | F | c.2335C>T | p.Arg779Cys | De novo | Unreported | AGS | Alive (4) |
| AGS2222 | P1 | M | c.2471G>A | p.Arg824Lys | De novo | Unreported | Isolated liver disease | Alive (9) |
| AGS2369 | P1 | M | c.1747A>G | p.Ile583Val | De novo | Unreported | AGS | Alive (10) |
| AGS2399 | P1 | M | c.2317G>C | p.Glu773Gln | De novo | Unreported | Neuroregression and SD starting at age 16 months | Alive (8) |
| AGS2422 | P1 | F | c.2159G>A | p.Arg720Gln | No parental testing | Unreported | SP | Alive (38) |
| AGS2507 | P1 | F | c.2335C>T | p.Arg779Cys | De novo | Unreported | AGS | Alive (1) |
| AGS2548 | P1 | M | c.2159G>A | p.Arg720Gln | De novo | Unreported | AGS | Alive (3) |
| AGS2586 | P1 | M | c.1178A>C | p.Asp393Ala | De novo | Unreported | AGS-like with frank regression at age 21 months | Alive (3) |
| AGS2662 (LD_1640) | P1 | F | c.2404A>G | p.Asn802Asp | De novo | Unreported | Neuroregression and SD starting at age 11 months | Alive (1) |
| AGS2669 | P1 | M | c.1331A>G | p.Glu444Gly | De novo | Unreported | AGS | Deceased (0.5) |
| Hm_1 | P1 | F | c.2156C>T | p.Ala719Val | De novo | Unreported | AGS | Alive (2) |
| Berg_1 | P1 | F | c.2336G>A | p.Arg779His | De novo | Unreported | Neuroregression and SD starting at age 9 months | Alive (7) |
| Orc_0098 | P1 | M | c.2336G>A | p.Arg779His | De novo | Unreported | AGS | Alive (4) |
| LD_0940.0 | P1 | M | c.2342G>A | p.Gly781Glu | De novo | Unreported | Neuroregression and SD starting at age 15 months | Alive (5) |
| LD_0943.0 | P1 | F | c.2342G>A | p.Gly781Glu | De novo | Unreported | SP | Alive (14) |
| LD_0982.0 | P1 | M | c.2159G>A | p.Arg720Gln | De novo | Adang et al. (2018); Case 2 | AGS | Alive (9) |
| LD_1030.0 | P1 | F | c.2335C>T | p.Arg779Cys | De novo | Unreported | AGS | Alive (5) |
| LD_1067.0 | P1 | M | c.2336G>T | p.Arg779Leu | De novo | Unreported | AGS | Alive (8) |
| LD_1199.0 | P1 | F | c.2336G>A | p.Arg779His | De novo | Unreported | AGS | Alive (4) |
| LD_1346.0 | P1 | M | c.2936T>G | p.Leu979Trp | De novo | Adang et al. (2018); Case 3 | AGS | Deceased (0.4) |
| LD_1381 (Hart) | P1 | F | c.2336G>A | p.Arg779His | Familial (4) | Unreported | SP | Alive (4) |
| P2 (brother of P1) | M | SP | Alive (3) | |||||
| P3 (father of P1 and P2) | M | SP | Alive (32) | |||||
| P4 (father of P3) | M | Clinically nonpenetrant | Alive (68) | |||||
| LD_1488.0 | P1 | F | c.2407A>T | p.Ile803Phe | De novo | Unreported | AGS | Alive (2) |
| LD_1585.0 | P1 | F | c.2336G>A | p.Arg779His | De novo | Unreported | AGS | Alive (5) |
Note: IFIH1 mutation annotation based on the reference complementary DNA sequence NM_022168.2.
Abbreviations: AGS, Aicardi–Goutières syndrome; CLL, Chilblain-like lesions; F, Female; ICC, intracranial calcification; LLD, Lupus-like disease; M, Male; SD, spastic dystonia; SP, spastic paraparesis; SMS: Singleton Merten syndrome; TM, transverse myelitis