Table 3.
Laterality defects and prevalence of two loss-of-function mutations by gene
| Ciliary Ultrastructure | Gene Mutation | SS | SIT | SA | Total (n) | 2 Loss-of-Function Mutations* |
|---|---|---|---|---|---|---|
| ODA defect | DNAH5 | 53 (34.6) | 75 (49) | 25 (16.3) | 153 | 86 (56.2) |
| DNAI1 | 14 (53.8) | 11 (42.3) | 1 (3.8) | 26 | 4 (15.4) | |
| CCDC103 † | 4 (28.6) | 7 (50) | 3 (21.4) | 14 | 0 | |
| DNAI2 | 7 (70) | 3 (30) | 0 | 10 | 8 (80) | |
| Other (CCDC114, ARMC4) | 6 (42.9) | 7 (50) | 1 (7.1) | 14 | 10 (71.4) | |
| No gene identified | 12 (48) | 10 (40) | 3 (12) | 25 | N/A | |
| ODA/IDA defect | SPAG1 | 6 (35.3) | 8 (47.1) | 3 (17.6) | 17 | 14 (82.4) |
| DNAAF4 | 11 (68.8) | 4 (25) | 1 (6.3) | 16 | 10 (62.5) | |
| DNAAF3 | 5 (45.5) | 6 (54.5) | 0 | 11 | 7 (63.6) | |
| DNAAF1 | 2 (22.2) | 6 (66.7) | 1 (11.1) | 9 | 5 (55.6) | |
| DNAAF5 | 4 (44.4) | 3 (33.3) | 2 (22.2) | 9 | 2 (22.2) | |
| LRRC6 | 5 (55.6) | 3 (33.3) | 1 (11.1) | 9 | 7 (77.8) | |
| Other (CFAP298, CFAP300, DNAAF2, PIH1D3, ZMYND10) | 5 (29.4) | 9 (52.9) | 3 (17.6) | 17 | 13 (76.5) | |
| No gene identified | 2 (25) | 4 (50) | 2 (25) | 8 | N/A | |
| IDA/MTD defect | CCDC40 | 26 (57.8) | 14 (31.1) | 5 (11.1) | 45 | 41 (91.1) |
| CCDC39 | 18 (47.4) | 18 (47.4) | 2 (5.3) | 38 | 31 (81.6) | |
| No gene identified | 8 (61.5) | 4 (30.8) | 1 (7.7) | 13 | N/A | |
| Normal ultrastructure associated with DNAH11 | DNAH11 | 19 (44.2) | 20 (46.5) | 4 (9.3) | 43 | 22 (51.2) |
| Normal/near-normal/other | HYDIN | 19 (100) | 0 | 0 | 19 | 19 (100) |
| RSPH4A | 16 (100) | 0 | 0 | 16 | 4 (25) | |
| RSPH1 | 15 (100) | 0 | 0 | 15 | 15 (100) | |
| CCNO | 9 (100) | 0 | 0 | 9 | 6 (66.7) | |
| Other (CCDC65, CCDC164, CFAP57, CFAP221, FOXJ1, GAS2L2, NEK10, OFD1, RPGR, RSPH3, RSPH9) | 20 (87) | 3 (13) | 0 | 23 | 19 (82.6) | |
| Total | 286 (51.2) | 215 (38.5) | 58 (10.4) | 559 | 323 (57.8) |
Definition of abbreviations: ARMC4 = armadillo repeat containing 4; CCDC39 = coiled-coil domain containing 39; CCDC40 = coiled-coil domain containing 40; CCDC65 = coiled-coil domain containing 65; CCDC103 = coiled-coil domain containing 103; CCDC114 = coiled-coil domain containing 114; CCDC164 = coiled-coil domain containing 164; CCNO = cyclin O; CFAP57 = cilia and flagella associated protein 57; CFAP221 = cilia and flagella associated protein 221; CFAP298 = cilia and flagella associated protein 298; CFAP300 = cilia and flagella associated protein 300; DNAAF1 = dynein axonemal assembly factor 1; DNAAF2 = dynein axonemal assembly factor 2; DNAAF3 = dynein axonemal assembly factor 3; DNAAF4 = dynein axonemal assembly factor 4; DNAAF5 = dynein axonemal assembly factor 5; DNAH5 = dynein axonemal heavy chain 5; DNAH11 = dynein axonemal heavy chain 11; DNAI1 = dynein axonemal intermediate chain 1; DNAI2 = dynein axonemal intermediate chain 2; FOXJ1 = forkhead box J1; GAS2L2 = growth arrest specific 2 like 2; HYDIN = hydrocephalus-inducing; IDA = inner dynein arm; LRRC6 = leucine-rich repeat containing protein 6; MTD = microtubular disorganization; N/A = not applicable; NEK10 = NIMA related kinase 10; ODA = outer dynein arm; OFD1 = orofaciodigital syndrome 1; PIH1D3 = PIH1 domain containing 3; RPGR = retinitis pigmentosa GTPase regulator; RSPH1 = radial spoke head component 1; RSPH3 = radial spoke head 3; RSPH4A = radial spoke head component 4A; RSPH9 = radial spoke head component 9; SA = situs ambiguus; SIT = situs inversus totalis; SPAG1 = sperm associated antigen 1; SS = situs solitus; ZMYND10 = zinc finger MYND-type containing 10.
Data are presented as n (%) unless otherwise noted.
Loss-of-function variants included nonsense, frameshift, start codon canonical splice site, large copy number changes, and full gene deletion variants. Not–loss-of-function mutations included missense, in-frame, and extended splice site (intronic and exonic) variants, which may be mild or have residual function.