Table 2.
Monogenic causes of rare non-Mendelian (typically sporadic) infectious diseases
| Infectious agent | Clinical phenotype | Immunological mechanism | Prevalence | Proportion explained |
|---|---|---|---|---|
| Neisseria | invasive disease | complement deficiency | 10−3–10−4 | 1%–5% |
| Streptococcus pneumoniae | invasive disease | TLR and IL-1R response deficiency | ∼10−4 | <5% |
| Staphylococcus aureus | invasive disease | TLR2 response deficiency IL-6 response deficiency | <10−5 | <1% |
| Tropheryma whipplei | Whipple’s disease | IRF4 deficiency | <10−6 | <1% |
| Herpes simplex virus 1 | encephalitis | TLR3-IFN-α/β deficiency snoRNA31 deficiency DBR1 deficiencya |
∼10−4 | 5%–10% |
| Human herpes virus 8 | endemic Kaposi sarcoma | OX40 deficiency | <10−5 | <1% |
| Cytomegalovirus | disseminated disease | NOS2 deficiency | <10−5 | <1% |
| Enterovirus | rhombencephalitis | TLR3/MDA5-IFN-α/β deficiency | <10−5 | <1% |
| Varicella zoster virus | encephalitis and pneumonia | POL3RA and POL3RC deficiency | <10−5 | <5% |
| Influenza | severe pneumonia | type I and III IFN deficiency | ∼10−5 | <1% |
| Rhinovirus | recurrent/severe infections | MDA5 deficiency | 10−4–10−5 | <5% |
| Human papillomavirus | recurrent respiratory papillomatosis | NLRP1 gain of function | ∼10−5 | <1% |
| Hepatitis A virus | fulminant hepatitis | IL-18BP deficiency | <10−5 | <1% |
| Live measles and yellow fever vaccines | severe infections | type I IFN response deficiency | <10−6 | <25% |
a
Inherited DBR1 deficiency underlies brainstem infection with HSV-1, influenza virus, or norovirus.