Original, non-overlapping findings of human digenic inheritance
| Disease | Gene/locus1 | Gene/locus2 | Replication | Reference(s) |
|---|---|---|---|---|
| Long QT syndrome (LQTS) | KCNH2/7q | KCNQ1/11p | Yes | 22 |
| LQTS | various LQT genes | various LQT genes | Yes | 23–26 |
| Deafness | GJB2/13q | GJB6/13q | DNA level | 9 |
| Deafness | TECTA/11q | 1p | No | 30 31 |
| Pendred syndrome/deafness | SLC26A4/7q | FOXI1/5q | No | 87 |
| Deafness suppression | 1q | 4q | No | 72 |
| Deafness | CDH23/10q | ATP2B2/3p | Partial | 49 |
| Usher syndrome | MYO7A/11q | 3q | No | 88 |
| Usher syndrome | CDH23/10q | PCDH15/10q | Yes | 27 |
| Usher syndrome | PDZD7/10q | GPR98/5q | Internal | 89 |
| Bartter's syndrome (antenatal w/deafness) | CLCNKA/1p | CLCNKB/1p | Yes | 90 |
| Bardet–Biedl syndrome | BBS2/16q | various BBS loci | Yes | 8 |
| Bardet–Biedl syndrome | BBS4/15q | various BBS genes | Yes | 61 |
| Bardet–Biedl syndrome | BBS1/11q | various BBS genes | Yes | 62 |
| Joubert syndrome (+ciliopathies) | CEP41/7q | various genes | No | 65 |
| Leber's congenital amaurosis(+ciliopathies) | CEP290/12q | MKKS/BBS6/20p | Internal | 66 |
| Short-rib polydactyly (ciliopathy) | NEK1/4q | DYNC2H1/11q | No | 67 |
| Nephrotic syndrome | NPHS1/19q | NPHS2/1q | Yes | 68 |
| Hypogonadotropic hypogonadism | PROKR2/20p | KAL1/Xp | Yes | 69 |
| Hypogonadotropic hypogonadism | FGFR1/8p | NSMF/9q | Yes | 70 |
| Hypogonadotropic hypogonadism | FGF8-related | FGF8-related | Internal | 71 |
| Hypogonadotropic hypo. (syndromic) | RNF216/7p | OTUD4/4q | No | 17 |
| Hirschsprung disease | RET/10q | EDNRB/13q | Yes | 91 |
| Parkinson's disease | PARK7/1p | PINK1/1p | No | 92 |
| Retinitis pigmentosa | PRPH2/6p | ROM1/11q | Internal | 7 |
| Glaucoma (earlier onset) | MYOC/1q | CYP1B1/2p | Yes | 93 |
| Waardenburg syndrome/albinism | MITF/3p | TYR/11q | Partial | 94 |
| Oculocutaneous albinism (OCA) | TYR/11q | OCA2/15q | Partial | 95 |
| Junctional epdermolysis bullosa | COL17A1/10q | LAMB3/1q | No | 96 |
| Disfibrinogenemia (slow clotting) | FGA/4q | FGG/4q | No | 97 |
| Polycystic kidney disease | PKD1/16p | PKD2/4q | No | 98 |
| Holoprosencephaly | SHH/7q | TGIF1/18p | Internal | 11 |
| Familial hypercholest. suppression | LDLR/19p | 13q | No | 73 |
| Cystinuria | SLC3A1/2p | SLC7A9/19q | Yes | 99 |
| Hyperinsulinemia | PPARG/3p | PPP1R3A/7q | No | 100 |
| Hypercholanemia | TJP2/9q | BAAT/9q | No | 79 |
| Pheochromocytoma | TMEM127/2q | 16p | No | 32 33 |
| Familial exudative vitreoretinopathy | FZD4/11q | F5/1q | No | 101 |
| Factor VIII thromboembolism | 5q | 11q | No | 102 |
| PMP22-related neuropathies | PMP22/17p | various genes | Partial | 103 104 |
| Charcot-Marie-Tooth disease (non-PMP22) | MFN2/1p | GDAP1/8q | No | 105 |
| Emery-Dreifuss muscular dystrophy | LMNA/1q | EMD/Xq | Yes | 106 |
| Porphyria (acute) | various genes | HFE/6p | Pathway level | 107 |
| Porphyria (acute) | UROD/1p | HMBS/11q | Pathway level | 108 |
| Porphyria (acute) | CPOX/3q | ALAD/9q | Pathway level | 109 |
| Epilepsy w/febrile seizures | 1q | 18q | No | 110 |
| Hemachromatosis | HFE/6p | HAMP/19q | No | 111 |
| Progressive external ophthalmoplegia | C10orf2/10q | POLG/15q | No | 112 |
| Epilepsy w/febrile seizures | SCN1A/2q | SCN2A/2q | No | 113 |
| Photosensitivity in epilepsy | 7q | 16p | No | 114 |
| Split-hand/foot malformation | 1q | 6q | No | 115 |
| Iminoglycinuria | SLC36A2/5q | SLC6A20/3p | Internal | 116 |
| Keratoconus | 1p | 8q | No | 117 |
| Limb-girdle muscular dystrophy | SGCB/4q | SGCD/5q | No | 118 |
| Ullrich congenital muscular dystrophy | COL6A1/21q | COL6A2/21q | No | 119 |
| Pseudoxanthoma elasticum | ABCC6/16p | GGCX/2p | No | 120 |
| Hereditary motor neuropathy | DSCL2/11q | 16p | No | 121 |
| Cleft lip | 1q | 2p | No | 122 |
| Fuchs corneal dystrophy | ZEB1/10p | 9p | No | 29 |
| Axenfeld–Rieger syndrome | PITX2/4q | FOXC1/6p | No | 123 |
| Colorectal cancer | MUTYH/1p | OGG1/3p | No | 124 |
| Rotor syndrome (hyperbilirubinemia) | SLCO1B1/12p | SLCO1B3/12p | Internal | 28 |
| Dent's disease | CLCN5/Xp | OCRL/Xq | No | 78 |
| Facioscapulohumeral musc. dystrophy | DUX4/4q | SMCHD1/18p | Internal | 16 |
| Epidermolysis bullosa simplex | KRT5/12q | KRT14/17q | No | 125 |
| Melanoma susceptibility | CDKN2A/9p | MC1R/16q | Yes | 21 |
| Hypotrichosis (nonsyndromic) | CDH3/16q | 12q | Internal | 75 |
A larger table including more rows with overlapping findings and more columns, such as the mode of inheritance at each locus, can be found in online supplementary table S1. Gene names are currently Hugo Genome Nomenclature Committee-approved names, not necessarily the gene names in the original publication. In some cases, the original study (eg, reference 11) reported multiple pairs of genes, and there is one representative pair in the table. Options for the Replication column (and their meanings) include: Yes (replicated in a later study), Internal (multiple pedigrees in the original study but no later study), Partial (one of the genes participates in some other documented human DI), Pathway level (other genes in the same pathway participate in other documented human DI), DNA level (applies only to GJB2/GJB6 and is explained in the text, No. Examples discussed in the text are put at the top of the Table. The replication references are given in online supplementary table S1.