Table 3. Clinical Phenotypes of Patients With Most Common XPF (ERCC4) and XPC Mutations.
| Patient No./Sex/Age, y | Gene | Mutation 1 | Mutation 2 | Sun Sensitivity | Abnormal Freckling | Neurologic Degeneration | Skin Cancer | DNA Repair Defect | DNA Repair Assay | Source(s) |
|---|---|---|---|---|---|---|---|---|---|---|
| XP72BR/M/18 | XPF (ERCC4) | p.P379S | Homozygous | Yes | Few lentigines | No | No | Yes | UDS, 35% | 12 |
| XP32BR/M/23 | XPF (ERCC4) | p.P379S | p.R589W | Yes | No | No | No | Yes | UDS, 18% | 12 |
| XP7NE/M/28a | XPF (ERCC4) | p.P379S | Silent | Yes | Yes | NA | No | Yes | UDS, 30% | 13 |
| XP126LO/F/22 | XPF (ERCC4) | p.R799W | p.T770Pfs*46 | Yes | Yes | No | No | Yes | UDS, 13% | 14, 15 |
| XP24BR/F/48 | XPF (ERCC4) | p.R799W | p.R589W | Yes | Few lentigines | Yes (adult onset) | No | Yes | UDS, 5% | 12, 16 |
| XP24KY/ Unknow/50 |
XPF (ERCC4) | p.R799W | 537fs+7bp | Unknown | Unknown | Yes (adult onset) | Unknown | Yes | UDS, 7% | 13 |
| XP48DC/F/51 (deceased) |
XPF (ERCC4) | p.R799W | p.F196Qfs*20 | Yes | Yes | Yes (began at 24 y) | Yes (BCC) | Yes | HCR, reduced | 17 |
| C014TA (sibling)/F/51 | XPF (ERCC4) | p.R799W | p.S459X | Yes | Yes | Yes (began at 30 y) | No | Yes | HCR, reduced | 17 |
| CO107TA (sibling)/M/51 (deceased) |
XPF (ERCC4) | p.R799W | p.S459X | Yes | Unknown | Yes (began at 42 y) | No | Yes | HCR, reduced | 17 |
| UDP-7356/F/54 (deceased) |
XPF (ERCC4) | p.R799W | p.S459X | Yes | Yes | Yes (chorea and ataxia at 34 y) | Yes (>20 BCC began at 16 y) | Yes | UDS, 21% | 18 |
| UDP-3675/F/60 | XPF (ERCC4) | p.R799W | p.R589W | Yes | Yes | Yes (cognitive impairment at 46 y) | No | Yes | UDS, 26% | 18 |
| XP42RO/M/62 | XPF (ERCC4) | p.R799W | Homozygous | Yes | Yes | Yes (began at 47 y) | Yes (9 at 27 y) | Yes | UDS, 20% | 13, 14 |
| XP62RO/ unknown |
XPF (ERCC4) | p.R799W | Homozygous | Unknown | Unknown | Yes (late onset?) | Unknown | Yes | UDS, 20% | 13 |
| XP26BR/F/41a | XPF (ERCC4) | p.R799W | L291X | Yes | Yes | Mild | No | Yes | UDS, 15% | 13 |
| XP1MI/F/17 (deceased) |
XPC | p.P334H | Homozygous | Yes | Yes | No | Yes | Yes | UDS, 29% | 19-22 |
Abbreviations: BCC, basal cell carcinoma; HCR, plasmid host cell reactivation after UV damage; NA, not available; UDS, unscheduled DNA synthesis after UV damage.
a
A. Lehmann, PhD, C. Arlett, PhD, H. Fassihi, MD, written communication, September 2018.