Table 3. Distribution of definite and probable pathogenic variants in 352 probands.
| Type of variant | PKD1 | PKD2 | |||
|---|---|---|---|---|---|
| Definite pathogenic | |||||
| Large rearrangements | 3 | 1% | 1 | 2% | |
| Frameshift | 92 | 30% | 10 | 19.5% | |
| Nonsense | 77 | 26% | 18 | 35% | |
| Canonic splicing | 24 | 8% | 10 | 19.5% | |
| In-frame ≥5 aminoacids | 4 | 1% | 0 | ||
| Probable pathogenic (HLP + LP) | |||||
| Missense | 75 | 25% | 9 | 18% | |
| In-frame <5 aminoacids | 20 | 7% | 1 | 2% | |
| Atypical splicing |
6 | 2% | 2 | 4% | |
|
Pathogenic variants spectra, comparison with previous large studies | |||||
| Present study n = 352* | CRISP n = 180* | GENKYST n = 442* | TGESP n = 188* | HALT-PKD CRISP n = 1034§ | |
| PKD1 | |||||
| truncating | 196 (55.7%) | 103 (57.2%) | 286 (64.7%) | 72 (38.3%) | 592 (57.3%) |
| nontruncating | 81 (23%) | 41 (22.8%) | 73 (16.5%) | 51 (27.1%) | 223 (21.6%) |
| IF indel | 24 (6.8%) | 9 (5%) | 29 (6.6%) | 8 (4.3%) | 54 (5.2%) |
| PKD2 | 51 (14.5%) | 27 (15%) | 54 (12.2%) | 57 (30.3%) | 165 (15.9%) |
| Classification of PKD1 and PKD2 variants and detection rates | |||||
| PKD1 | PKD2 | PKD1 + PKD2 | |||
| DP | HLP + LP | DP | HLP + LP | ||
| Familial (n = 320) | 154 (48%) | 73 (23%) | 33 (10%) | 6 (2%) | 266 (83%) |
| Sporadic (n = 120) | 46 (38%) | 28 (24%) | 6 (5%) | 6 (5%) | 86 (72%) |
| Total DP | 200 | 39 | 239 (54%) | ||
| Total HLP + LP | 101 | 12 | 113 (26%) | ||
| Total PKD1 301 (85.5%) | Total PKD2 51 (14.5%) | 352 (80%) | |||
°All in-frame indels grouped together.
*Total probands/families with pathogenic variants.
§Total patients with pathogenic variants truncating: frameshift, nonsense, canonic splice site, large rearrangements nontruncating: missense, atypical splicing.
DP: definite pathogenic; HLP: highly likely pathogenic; LP: likely pathogenic.