Table 4.
Summary of PKD1 Mutation Changes Identified in the Study Population
Designation | Location | cDNAChange(s) | AminoAcidChangea | Comments | Pedigree(s) | Reference(s) |
Nonsense: | ||||||
S225X | EX5 | 885C→A | 225↓ | At CpG | P499 | Present study |
Q227X | EX5 | 890C→T | 227↓ | P408 | Present study | |
Q705X | EX11 | 2324C→T | 705↓ | P255 | Present study | |
S749X | EX11 | 2457C→G | 749↓ | P398 | Present study | |
E1537X | EX15 | 4820G→T | 1537↓ | At CpG | P18 | Present study |
R2163X | EX15 | 6698C→T | 2163↓ | C→T at CpG | P126 | Present study |
C2229X | EX15 | 6898C→A | 2229↓ | P13, P404 | Present study | |
Q2243X | EX15 | 6938C→T | 2243↓ | P17, P17A | Present study | |
C2370X | EX17 | 7321T→A | 2370↓ | P7 | Present study | |
R2430X | EX18 | 7499C→T | 2430↓ | C→T at CpG, matches HG 1, 2, and 3 | P227, P344 | Present study |
E3020X | EX25 | 9269G→T | 3020↓ | At CpG | P130 | Peral et al. (1997) |
W3180X | EX27 | 9751G→A | 3180↓ | P322 | Present study | |
Q3394X | EX32 | 10391C→T | 3394↓ | P292 | Present study | |
Q3513X | EX35 | 10748C→T | 3513↓ | P105, P187 | Peral et al. (1997); present study | |
Y3818X | EX41 | 11665C→A | 3818↓ | At CpG | P117 | Peral et al. (1996a) |
Q3837X | EX41 | 11720C→T | 3837↓ | P198 | Peral et al. (1996b) | |
R4020X | EX44 | 12269C→T | 4020↓ | C→T at CpG | P264 | Present study |
Y4039X | EX44 | 12328C→A | 4039↓ | At CpG | P407 | Present study |
Q4041X | EX44 | 12332C→T | 4041↓ | P284 | Torra et al. (1998) | |
R4227X | EX46 | 12890C→T | 4227↓ | C→T at CpG | P3, P89, P252 | Peral et al. 1996b, 1997); present study |
Deletion or insertion: | ||||||
Frameshift: | ||||||
224del13 | EX1 | 224del13 | 4↓ | 8-bp repeat 13 bp apart | P103 | Present study |
2296delC | EX10 | 2296delC | 695↓ | 6 × C nt | P99 | Present study |
2296insC | EX10 | 2296insC | 695↓ | 6 × C nt | P399 | Present study |
4137delCT | EX15 | 4137delCT | 1308↓ | P234 | Present study | |
4291delG | EX15 | 4291delG | 1360↓ | P184 | Present study | |
4784delG | EX15 | 4784delG | 1524↓ | P314 | Present study | |
5870del14 | EX15 | 5870del14 | 1886↓ | 7-bp repetition, 14 bp apart | P236 | Present study |
6937delAC | EX15 | 6937delAC | 2242↓ | 2 × AC repeats | P107, P224 | Present study |
7205del7 | EX15 | 7205del7 | 2331↓ | 7-bp direct repeat | P2, P216 | Present study |
7211ins7 | EX16 | 7211ins7 | 2333↓ | 7-bp direct repeat | P169, P200 | Present study |
7324delGT | EX17 | 7324delGT | 2371↓ | 4 × GT repeats | P8 | Present study |
8126ins20 | EX21 | 8126ins20 | 2638↓ | 9×bp repeat, 20 bp apart | P118 | Present study |
8657delC | EX23 | 8657delC | 2815↓ | 3 × C nt | P179 | Peral et al. (1997) |
9299delC | EX25 | 9299delC | 3029↓ | P11 | Peral et al. (1997) | |
IVS30del2 kb | IVS30−IVS34 | 10262del446 | 3350↓ | P98 | European Polycystic Kidney Disease Consortium (1994) | |
IVS34del5.5 kb | IVS34−3′UTR | 10708del to 3′UTR | 3499↓ | P95 | European Polycystic Kidney Disease Consortium (1994) | |
10947insT | EX36 | 10947insT | 3578↓ | P100 | Peral et al. (1996a) | |
12617delC | EX45 | 12617delC | 4135↓ | P491 | Present study | |
12739delA | EX46 | 12739delA | 4176↓ | Flanked by 5 × C/3 × C | P225 | Peral et al. (1997) |
In frame: | ||||||
F1992L, 1993delT | EX15 | 6187delC | 1992*Δ1993 | P204 | Present study | |
6868del15 | EX15 | 6868del15 | Δ2220–2224 | 13-bp repeat, 15 bp apart | P14 | Present study |
8507ins12 | EX23 | 8507dup12 | +2762–2765 | 10-bp repeat, 12 bp apart | P190 | Present study |
9245del18 | EX25 | 9245del18 | Δ3012–3017 | Incomplete repeat (13/18), 18 bp apart | P124 | Present study |
11457del15 | EX39 | 11457del15 | Δ3749–3753 | 7-bp repeat, 15 bp apart | P35 | Peral et al. (1996b) |
Splicing: | ||||||
Frameshift: | ||||||
IVS7+1G→A | IVS7 | 1597del221 | 536↓ | Skip exon 7 | P1 | Present study |
IVS9+1G→T | IVS9 | 1934del127 | 574↓ | Skip exon 9 | P134 | Present study |
IVS25−16G→A | IVS25 | 9413del196 | 3067↓ | Skip exon 26, C→T at CpG | P178 | Present study |
IVS31+25del9 | IVS31 | 10378ins71 | 3389↓ | Inclusion IVS 31, matches HG1, 12-bp repeat, 19 bp apart | P229 | Peral et al. (1997) |
IVS39+1G→C | IVS39 | 11365del113 | 3717↓ | Skip exon 39 | P109 | Peral et al. (1997) |
In frame: | ||||||
IVS2−2A→G | IVS2 | 499del72 | Δ97–120 | Skip exon 3 | P402 | Present study |
IVS21−2delAG | IVS21 | 8228del42 | Δ2673–2686 | Cryptic splice exon 22 | P152 | Present study |
IVS39−25del72 | IVS39 | 11478del51 | Δ3756–3772 | 5-bp repeat 67 bp apart; cryptic splice exon 40 | P167 | Peral et al. (1996b) |
IVS43+17del18 | IVS43 | 11921del291 + others | Δ3904–4000 + others | 9-bp repeat 20 bp apart | S6046 | Peral et al. (1995) |
IVS43+14del20 | IVS43 | 11921del291 + others | Δ3904–4000 + others | 9-bp repeat 20 bp apart | P138 | Peral et al. (1995) |
IVS44+1G→C | IVS44 | 12212del135 | Δ4001–4045 | Skip exon 44 | P4 | European Polycystic Kidney Disease Consortium (1994) |
Missense: | ||||||
Nonconservative: | ||||||
L13Q | EX1 | 249T→A | L13Q | P285 | Present study | |
S75F | EX2 | 435C→T | S75F | P159 | Present study | |
W139C | EX4 | 628G→T | W139C | P267 | Present study | |
Y2336D | EX16 | 7217T→G | Y2336D | P220 | Present study | |
A2752D | EX23 | 8466C→A | A2752D | P135 | Present study | |
V2768M | EX23 | 8513G→A | V2768M | C→T at CpG | P442 | Present study |
G2858S | EX23 | 8783G→A | G2858S | C→T at CpG | P442 | Present study |
E2771K | EX23 | 8522G→A | E2771K | C→T at CpG | P148, P256, P447, P511 | Present study |
L2816P | EX23 | 8658T→C | L2816P | Matches HG1, 2, and 3 | P228 | Present study |
L2993P | EX25 | 9189T→C | L2993P | P193 | Peral et al. (1997) | |
Q3016R | EX25 | 9258A→G | Q3016R | P157 | Peral et al. (1997) | |
Conservative: | ||||||
L3510V | EX35 | 10739C→G | L3510V | P161 | Peral et al. (1997) | |
E3631D | EX37 | 11104G→C | E3631D | P125 | Peral et al. (1996b) |
↓ = Frameshift after indicated residue; Δ = deletion of indicated residues (inclusive); + = duplication of indicated residues (inclusive).