Table 1.
Examples of phenocopies in human diseases. This is a table illustrating examples of phenocopies in different fields of medicine. For each disease, we report disease-causing genes (when known), phenocopies and corresponding mechanisms.
| Disease (Phenotype) | Causative Gene/s | Phenocopy | Mechanism of Phenocopy Determination | Ref. |
|---|---|---|---|---|
| Pendred’s syndrome | SLC26A4 | Endemic cretinism | Environmental | [34] |
| Monogenic skeletal disorders (e.g., Holt–Oram syndrome, radius aplasia-thrombocytopenia syndrome) | e.g., TBX5, RBM8A | Thalidomide embryopathy | Environmental | [34,38] |
| North Carolina macular dystrophy (NCMD) grade 3 | locus chr5p15-p13 | Congenital toxoplasmosis | Environmental | [41] |
| North Carolina macular dystrophy (NCMD) grade 1 | DHS6S1 | Foveal hypoplasia | Unknown | [41] |
| North Carolina macular dystrophy (NCMD) grade 2 | PROM1 | Torpedo maculopathy | Unknown | [41] |
| Hypertrophic cardiomyopathy | Sarcomeric genes | Glycogen storage diseases (e.g., Danon disease) | Monogenic | [42,43,44] |
| Lisosomal storage diseases (e.g., Fabry disease) | Monogenic | |||
| Mitocondrial cytopathies (e.g., MELAS) | Monogenic | |||
| AL amyloidosis | Unknown | |||
| Autoimmune lymphoproliferative syndrome (ALPS) | FAS, FASLG, CASP10 | ALPS phenocopies | Somatic mutations in FAS (non-Mendelian genetic mechanism) | [47,48,49] |
| Cryopyrinopathies | NLRP3 | Cryopyrinopathies phenocopies | Somatic mutations in NLRP3 (non-Mendelian genetic mechanism) | [47] |
| Hereditary angioedema | SERPING1 | Acquired angioedema | Autoantibodies anti-C1-inhibitor (complex mechanism) | [50] |
| Chronic mucocutaneous candidiasis | Genes encoding IL-17, IL-22 | Recurrent fungal infections | Autoantibodies anti-IL17 or IL-22 (complex mechanism) | [51] |
| Familial Parkinson’s disease | SNCA, LRRK2, PRKN, PINK1 and others | Familial Parkinson’s disease negative for mutations in known genes | Unknown | [53,54] |
| Familial breast cancer | BRCA1, BRCA2 | Familial breast cancer negative for mutations in BRCA genes | Unknown (probably genetic) | [56,57] |
| Huntington disease (HD) | HTT | HD phenocopies | Monogenic (mutations in genes different from HTT) | [58,59] |
| Brugada syndrome | SCN5A | Brugada phenocopies (e.g., metabolic abnormalities, ischemia, mechanic compression, myocardial and pericardial diseases) | Unknown (probably complex) | [60,61,62] |