Genetic and clinical characteristics of reported patients harboring TLR7 mutations leading to enhanced TLR7 signaling
| Reference (identifier) . | Mutation (inheritance) . | Inheritance . | Sex . | Age at presentation . | Autoimmunity . | Neurological disease . |
|---|---|---|---|---|---|---|
| (5) (family A) | c.790T > C/Y264H | De novo | F | 7 years | SLE | Relapsing hemichorea |
| (5) (family B: mother) | c.1521T > G/F507L | Unknown | F | 25 yearsa | SLE | Hemiplegic “CP”a |
| (5) (family B: proband) | c.1521T > G/F507L | Maternal | F | 9 years | AQP4+ NMO | AQP4+ NMO |
| (5) (family C) | c.82A > G/R28G | Unknown | F | 18 years | SLE | No |
| (6) (AGS571: proband) | c.1520T > C/F507S | Maternal | F | 4 years | SLE | Cerebral vasculitis |
| (6) (AGS571: brother) | c.1520T > C/F507S | Maternal | M | 2 days | Not reported | AGS-like |
| (6) (AGS571: mother) | c.1520T > C/F507S | Unknown | F | 12 years | Probable SLE | Not reported |
| (6) (AGS3740) | c.1582C > A/L528I | De novo | F | 1 year | Evans syndrome | AGS-like |
| (7) | c.800C > T/P267L | De novo | F | 13 mo | Anti-NMDA encephalitis + SLE | Anti-NMDA encephalitis |
| (8) | c.2453G > T/G818V | De novo | F | 8 mo | Evans syndrome | No |
| (9) | c.1517T > C/F506S | De novo (somatic) | M | 15 days | SLE | ICC |
| (10) | c.1520G > T/F507S | De novo | F | 1 mo | ITP, SLE | GDD, WMD |
| (11) | c.1303C > T/P435S | De novo | F | 2 years | SLE | Spasticity |
| (12) (proband)b | c.2519T > G/L840R | Maternal | M | 3 years | SLE | No |
| (12) (mother)b | c.2519T > G/L840R | Unknown | F | No clinical data | No clinical data | No clinical data |
| Reference (identifier) . | Mutation (inheritance) . | Inheritance . | Sex . | Age at presentation . | Autoimmunity . | Neurological disease . |
|---|---|---|---|---|---|---|
| (5) (family A) | c.790T > C/Y264H | De novo | F | 7 years | SLE | Relapsing hemichorea |
| (5) (family B: mother) | c.1521T > G/F507L | Unknown | F | 25 yearsa | SLE | Hemiplegic “CP”a |
| (5) (family B: proband) | c.1521T > G/F507L | Maternal | F | 9 years | AQP4+ NMO | AQP4+ NMO |
| (5) (family C) | c.82A > G/R28G | Unknown | F | 18 years | SLE | No |
| (6) (AGS571: proband) | c.1520T > C/F507S | Maternal | F | 4 years | SLE | Cerebral vasculitis |
| (6) (AGS571: brother) | c.1520T > C/F507S | Maternal | M | 2 days | Not reported | AGS-like |
| (6) (AGS571: mother) | c.1520T > C/F507S | Unknown | F | 12 years | Probable SLE | Not reported |
| (6) (AGS3740) | c.1582C > A/L528I | De novo | F | 1 year | Evans syndrome | AGS-like |
| (7) | c.800C > T/P267L | De novo | F | 13 mo | Anti-NMDA encephalitis + SLE | Anti-NMDA encephalitis |
| (8) | c.2453G > T/G818V | De novo | F | 8 mo | Evans syndrome | No |
| (9) | c.1517T > C/F506S | De novo (somatic) | M | 15 days | SLE | ICC |
| (10) | c.1520G > T/F507S | De novo | F | 1 mo | ITP, SLE | GDD, WMD |
| (11) | c.1303C > T/P435S | De novo | F | 2 years | SLE | Spasticity |
| (12) (proband)b | c.2519T > G/L840R | Maternal | M | 3 years | SLE | No |
| (12) (mother)b | c.2519T > G/L840R | Unknown | F | No clinical data | No clinical data | No clinical data |
Bold indicates familial cases.
CP, cerebral palsy; F, female; GDD, global developmental delay; ICC, intracranial calcification; ITP, immune thrombocytopenia; M, male; WMD, white matter disease.
While SLE did not manifest until age 25 years, it is possible that the cerebral palsy diagnostic label may be incorrect and the patient's phenotype directly linked to the mutation in TLR7.
Note, a brother to the proband is reported to have presented at age 1 year with hemolytic anemia and was subsequently diagnosed with SLE at age 19 years, dying at age 29 years due to a cerebrovascular accident related to the underlying SLE. No genotyping was undertaken in this individual.