Table 3.
IRF6 exonic mutations in unrelated families with VWS and PPS.
Diagnosisa | Mutation | ntb | nt changec | aa changed | exone | Originf | Citation |
---|---|---|---|---|---|---|---|
VWS | truncation | -219 | C>T | 0? | 1 | Brazil | This study |
VWS | truncation | -151 | G>A | 0? | 1 | Brazil | This study |
VWS | truncation | -151 | G>A | 0? | 1 | N Eur | This study |
VWS | truncation | -151 | G>A | 0? | 1 | N Eur | This study |
NS | truncation | -48 | A>T | 0? | 2 | NS | This study |
VWS | truncation | -48 | A>T | 0? | 2 | N Eur | 14 |
VWS | truncation | -19 | C>A | 0? | 2 | NS | This study |
VWS | truncation | 1 | A>G | 0? | 3 | Brazil | This study |
VWS | truncation | 3 | G>A | 0? | 3 | N Eur | 14 |
VWS | missense | 5 | C>T | Ala2Val | 3 | N Eur | 14 |
VWS | missense | 16 | C>T | Arg6Cys | 3 | Brazil | 14 |
VWS | missense | 16 | C>T | Arg6Cys | 3 | Brazil | This study |
VWS | truncation | 16 | del C | Arg6AlafsX3 | 3 | NS | This study |
VWS | truncation | 16_17 | ins C | Arg6ProfsX13 | 3 | N Eur | This study |
VWS | missense | 17 | G>T | Arg6Leu | 3 | N Eur | This study |
VWS | missense | 17 | G>C | Arg6Pro | 3 | N Eur | This study |
NS | missense | 26 | G>A | Arg9Gln | 3 | NS | This study |
VWS | missense | 26 | G>A | Arg9Gln | 3 | Brazil | This study |
VWS | missense | 35 | C>T | Pro12Leu | 3 | N Eur | This study |
VWS | missense | 39 | G>T | Trp13Cys | 3 | Brazil | This study |
VWS | truncation | 43_44 | ins ATAG | Val15AspfsX5 | 3 | NS | This study |
VWS | missense | 47 | C>T | Ala16Val | 3 | Belgium | 21 |
VWS | truncation | 49_64 | del | Gln17SerfsX23 | 3 | N Eur | 14 |
VWS | missense | 50 | A>G | Gln17Arg | 3 | Brazil | This study |
VWS | missense | 52 | G>A | Val18Met | 3 | N Eur | 14 |
VWS | missense | 53 | T>C | Val18Ala | 3 | N Eur | 14 |
VWS | missense | 56 | A>G | Asp19Gly | 3 | Germany | This study |
VWS | missense | 58 | G>A | Ser20Asn | 3 | NS | This study |
PPS | missense | 65 | T>C | Leu22Pro | 3 | Belgium | 21 |
VWS | truncation | 69 | C>A | Tyr23X | 3 | N Eur | 14 |
VWS | missense | 71 | C>T | Pro24Leu | 3 | N Eur | This study |
VWS | missense | 74 | G>T | Gly25Val | 3 | Belgium | This study |
VWS | missense | 83 | G>T | Trp28Leu | 3 | Brazil | This study |
VWS | truncation | 99 | dup T | Lys34X | 3 | N Eur | This study |
VWS | missense | 101 | A>C | Lys34Thr | 3 | NS | This study |
VWS | missense | 104 | G>C | Arg35Pro | 3 | Brazil | This study |
VWS | missense | 107 | T>C | Phe36Ser | 3 | N Eur | This study |
VWS | missense | 115 | C>G | Pro39Ala | 3 | N Eur | 14 |
VWS | truncation | 136 | del C | His46IlefsX15 | 3 | N Eur | This study |
VWS | truncation | 154 | G>T | Glu52X | 3 | N Eur | This study |
VWS | Truncation | 161 | dup A | Asn54LysfsX3 | 3 | Germany | This study |
VWS | missense | 167 | T>C | Ile56Thr | 3 | Brazil | This study |
PPS | splicing | 174 | G>A (80%>8%) | p.? | 3 | NS | This study |
VWS | missense/splicing | 175 | G>T (58%>8%) | p.? | 4 | Brazil | This study |
PPS | missense | 178 | T>G | Trp60Gly | 4 | N Eur | 14 |
VWS | missense | 180 | G>T | Trp60Cys | 4 | Brazil | This study |
VWS | missense | 181 | G>A | Ala61Thr | 4 | NS | This study |
VWS | missense | 182 | C>G | Ala61Gly | 4 | N Eur | 14 |
VWS | missense | 191 | T>C | Thr64Ile | 4 | Belgium | 21 |
PPS | missense | 197 | A>C | Lys66Thr | 4 | N Eur | 14 |
VWS | missense | 197_199 | delinsGGG | Lys66_Tyr67delinsArgAsp | 4 | N Eur | This study |
PPS | missense | 200 | A>G | Tyr67Cys | 4 | Belgium | This study |
VWS | Truncation | 201 | C>A | Tyr67X | 4 | Germany | 16 |
VWS | truncation | 202 | C>T | Gln68X | 4 | N Eur | 14 |
VWS | truncation | 202 | C>T | Gln68X | 4 | N Eur | 14 |
VWS | missense | 208 | G>C | Gly70Arg | 4 | N Eur | 14 |
VWS | missense | 208 | G>C | Gly70Arg | 4 | N Eur | 14 |
VWS | missense | 221 | C>T | Pro74Leu | 4 | Brazil | This study |
VWS | missense | 221 | C>T | Pro74Leu | 4 | Brazil | This study |
VWS | missense | 221 | C>G | Pro74Arg | 4 | N Eur | This study |
VWS | duplication | 223_240 | dup | Asp75_Lys80dup | 4 | N Eur | This study |
VWS | missense | 226 | C>T | Pro76Ser | 4 | N Eur | 14 |
VWS | missense | 230 | C>A | Ala77Asp | 4 | Brazil | This study |
PPS | missense | 244 | C>A | Gln82Lys | 4 | N Eur | 14 |
VWS | missense | 246 | G>C | Gln82His | 4 | Brazil | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | Belgium | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | Belgium | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | Brazil | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | NS | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | NS | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | Germany | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | 14 |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | 14 |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | 14 |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | This study |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | 14 |
PPS | missense | 250 | C>T | Arg84Cys | 4 | N Eur | 14 |
VWS | missense | 250 | C>T | Arg84Cys | 4 | Brazil | This study |
VWS | missense | 250 | C>T | Arg84Cys | 4 | Brazil | This study |
VWS | missense | 250 | C>T | Arg84Cys | 4 | NS | This study |
PPS | missense | 251 | G>A | Arg84His | 4 | NS | This study |
PPS | missense | 251 | G>A | Arg84His | 4 | NS | This study |
PPS | missense | 251 | G>A | Arg84His | 4 | N Eur | 14 |
PPS | missense | 251 | G>A | Arg84His | 4 | N Eur | This study |
PPS | missense | 251 | G>A | Arg84His | 4 | N Eur | 14 |
PPS | missense | 251 | G>A | Arg84His | 4 | Belgium | This study |
VWS | missense | 251 | G>A | Arg84His | 4 | Belgium | This study |
VWS | missense | 251 | G>A | Arg84His | 4 | N Eur | This study |
VWS | missense | 251 | G>C | Arg84Pro | 4 | Belgium | This study |
VWS | missense | 251 | G>C | Arg84Pro | 4 | UK | This study |
VWS | missense | 259 | C>T | Leu87Phe | 4 | Brazil | This study |
VWS | missense | 259 | C>T | Leu87Phe | 4 | Brazil | This study |
NS | missense | 262 | A>T | Asn88Tyr | 4 | NS | This study |
VWS | missense | 262 | A>C | Asn88His | 4 | Brazil | This study |
VWS | missense | 262 | A>C | Asn88His | 4 | N Eur | 14 |
VWS | missense | 263 | A>G | Asn88Ser | 4 | N Eur | This study |
PPS | missense | 265 | A>G | Lys89Glu | 4 | N Eur | 14 |
VWS | missense | 265 | A>G | Lys89Glu | 4 | Brazil | This study |
VWS | missense | 268 | A>G | Ser90Gly | 4 | N Eur | 14 |
VWS | missense | 269 | G>T | Ser90Ile | 4 | Belgium | This study |
VWS | missense | 274 | G>A | Glu92Lys | 4 | Brazil | This study |
VWS | missense | 274 | G>A | Glu92Lys | 4 | Brazil | This study |
VWS | missense | 274 | G>A | Glu92Lys | 4 | Brazil | This study |
VWS | truncation | 274 | G>T | Glu92X | 4 | Brazil | This study |
VWS | truncation | 274 | G>T | Glu92X | 4 | N Eur | 14 |
VWS | missense | 284 | T>C | Leu95Pro | 4 | N Eur | This study |
VWS | missense | 292 | G>C | Asp98His | 4 | N Eur | 14 |
VWS | missense | 293 | A>G | Asp98Gly | 4 | Brazil | This study |
VWS | missense | 298 | A>G | Thr100Ala | 4 | Belgium | 21 |
VWS | missense | 299 | C>T | Thr100Ile | 4 | N Eur | This study |
VWS | missense | 328 | A>T | Ile110Leu | 4 | Belgium | This study |
VWS | missense | 332 | A>G | Tyr111Cys | 4 | Brazil | This study |
VWS | missense | 332 | A>G | Tyr111Cys | 4 | Brazil | This study |
VWS | missense | 332 | A>G | Tyr111Cys | 4 | N Eur | This study |
VWS | truncation | 352 | C>T | Gln118X | 4 | NS | This study |
VWS | truncation | 352 | C>T | Gln118X | 4 | N Eur | 14 |
VWS | missense | 358 | C>A | Gln120Lys | 4 | N Eur | This study |
VWS | truncation | 358 | C>T | Gln120X | 4 | N Eur | This study |
VWS | truncation | 358_368 | del | Gln120HisfsX | 4 | Thailand | 23 |
VWS | truncation | 405_406 | ins TT | Asp135_Glu136LeufsX31 | 5 | Germany | This study |
VWS | truncation | 427 | G>T | Glu143X | 5 | N Eur | This study |
VWS | truncation | 466 | dup C | His156ProfsX39 | 5 | N Eur | 14 |
VWS | missense | 470 | T>G | Val157Gly | 5 | Brazil | This study |
VWS | truncation | 494 | del T | Phe165SerfsX | 5 | N Eur | This study |
VWS | truncation | 522_525 | del | Ala174fsX47 | 6 | Belgium | This study |
VWS | truncation | 558 | C>A | Cys186X | 6 | N Eur | 14 |
VWS | truncation | 576 | G>A | Try192X | 6 | N Eur | 14 |
VWS | truncation | 576 | G>A | Try192X | 6 | Germany | This study |
VWS | truncation | 554_579 | dup | Lys194AsnfsX23 | 6 | Brazil | This study |
VWS | missense | 589 | C>T | Pro197Ser | 6 | Brazil | This study |
VWS | truncation | 610 | del C | Gln204ArgfsX18 | 6 | N Eur | This study |
VWS | truncation | 610 | C>T | Gln204X | 6 | Brazil | This study |
VWS | truncation | 610 | C>T | Gln204X | 6 | N Eur | This study |
VWS | truncation | 610 | C>T | Gln204X | 6 | N Eur | This study |
VWS | truncation | 634_635 | ins CCAC | Ser212ThrfsX14 | 6 | N Eur | 14 |
PPS | truncation | 651 | G>A | Try217X | 6 | N Eur | This study |
VWS | truncation | 657_665 | delins TA | Ser219fsX1 | 6 | N Eur | 14 |
VWS | missense | 665 | C>T | Pro222Leu | 6 | N Eur | This study |
VWS | truncation | 706 | G>T | Glu236X | 7 | Brazil | This study |
VWS | truncation | 722_723 | ins C | Met241IlefsX19 | 7 | Brazil | This study |
VWS | missense | 743 | G>C | Gly248Ala | 7 | N Eur | This study |
VWS | truncation | 744_748 | del | Gly248fsX10 | 7 | N Eur | 14 |
VWS | missense | 748 | C>G | Arg250Gly | 7 | Brazil | This study |
VWS | missense | 748 | C>G | Arg250Gly | 7 | Brazil | This study |
VWS | missense | 748 | C>G | Arg250Gly | 7 | N Eur | This study |
VWS | truncation | 748 | C>T | Arg250X | 7 | Belgium | This study |
VWS | truncation | 748 | C>T | Arg250X | 7 | N Eur | This study |
VWS | truncation | 748 | C>T | Arg250X | 7 | Belgium | This study |
VWS | missense | 749 | G>A | Arg250Gln | 7 | Brazil | This study |
VWS | missense | 749 | G>A | Arg250Gln | 7 | Brazil | This study |
VWS | missense | 749 | G>A | Arg250Gln | 7 | N Eur | 14 |
VWS | missense | 749 | G>A | Arg250Gln | 7 | N Eur | This study |
VWS | missense | 749 | G>A | Arg250Gln | 7 | N Eur | This study |
VWS | missense | 755 | T>C | Leu251Pro | 7 | Belgium | 21 |
VWS | truncation | 759 | T>A | Tyr253X | 7 | N Eur | 14 |
VWS | missense | 775 | C>T | Pro258Ser | 7 | Belgium | 21 |
VWS | truncation | 784 | C>T | Gln262X | 7 | Brazil | This study |
VWS | truncation | 795 | del C | Leu265fsX36 | 7 | N Eur | 14 |
VWS | missense | 803 | C>T | Pro268Leu | 7 | Brazil | This study |
VWS | missense | 818 | A>G | Gln273Arg | 7 | N Eur | 14 |
VWS | truncation | 842 | del A | His281LeufsX20 | 7 | N Eur | 14 |
VWS | deletion | 870_897 | del/ins A | Phe290_Asp296delinsLeu | 7 | N Eur | 14 |
VWS | missense | 881 | T>C | Leu294Pro | 7 | N Eur | 14 |
VWS | missense | 889 | G>A | Val297Ile | 7 | N Eur | 14 |
VWS | missense | 905 | T>C | Leu302Pro | 7 | Brazil | This study |
VWS | missense | 953 | A>C | Gln318Pro | 7 | N Eur | This study |
VWS | missense | 954 | G>C | Gln318His | 7 | NS | This study |
VWS | missense | 955 | T>C | Cys319Arg | 7 | N Eur | This study |
VWS | truncation | 957 | C>A | Cys319X | 7 | Brazil | This study |
VWS | truncation | 957 | C>A | Cys319X | 7 | Brazil | This study |
VWS | missense | 958 | A>G | Lys320Glu | 7 | N Eur | 14 |
VWS | missense | 958 | A>G | Lys320Glu | 7 | N Eur | 14 |
VWS | missense | 961 | G>A | Val321Met | 7 | Belgium | This study |
VWS | missense | 961 | G>A | Val321Met | 7 | N Eur | 14 |
VWS | missense | 965 | A>G | Tyr322Cys | 7 | Brazil | This study |
VWS | missense | 974 | G>A | Gly325Glu | 7 | Belgium | This study |
VWS | missense | 974 | G>A | Gly325Glu | 7 | N Eur | 14 |
VWS | Truncation | 1011_1020 | del | Ile337fsX22 | 7 | Germany | This study |
VWS | missense | 1034 | T>C | Leu345Pro | 7 | N Eur | 14 |
VWS | missense | 1040 | G>T | Cys347Phe | 7 | N Eur | 14 |
VWS | truncation | 1087 | del A | Ile363X | 8 | N Eur | This study |
VWS | missense | 1106 | T>C | Phe369Ser | 8 | N Eur | This study |
VWS | truncation | 1107 | del T | Phe369LeufsX27 | 8 | N Eur | 14 |
VWS | truncation | 1116 | C>G | Tyr372X | 8 | N Eur | This study |
VWS | missense | 1118 | T>C | Leu373Ser | 8 | Brazil | This study |
VWS | missense | 1120 | T>C | Cys374Arg | 8 | Brazil | This study |
VWS | missense | 1122 | C>G | Cys374Try | 8 | N Eur | 14 |
VWS | missense | 1123 | T>C | Phe375Leu | 8 | Brazil | This study |
VWS | missense | 1126 | G>C | Gly376Arg | 8 | Brazil | This study |
VWS | missense | 1126 | G>C | Gly376Arg | 8 | N Eur | This study |
VWS | truncation | 1136 | G>A | Try379X | 8 | Brazil | This study |
VWS | truncation | 1136 | G>A | Try379X | 8 | Brazil | This study |
VWS | missense | 1162 | A>G | Lys388Glu | 8 | N Eur | 14 |
PPS | truncation | 1177 | C>T | Gln393X | 8 | N Eur | 14 |
VWS | missense | 1190 | T>C | Val397Ala | 9 | NS | This study |
VWS | missense | 1198 | C>T | Arg400Try | 9 | Belgium | This study |
VWS | missense | 1198 | C>T | Arg400Try | 9 | Brazil | This study |
VWS | missense | 1198 | C>T | Arg400Try | 9 | Brazil | This study |
VWS | missense | 1198 | C>T | Arg400Try | 9 | Brazil | This study |
VWS | missense | 1198 | C>T | Arg400Try | 9 | Brazil | This study |
VWS | missense | 1198 | C>T | Arg400Try | 9 | Brazil | This study |
VWS | missense | 1199 | G>A | Arg400Gln | 9 | Brazil | This study |
VWS | missense | 1210 | G>A | Glu404Lys | 9 | Brazil | This study |
VWS | missense | 1212_1226 | del | Glu404_Gly408delAsp | 9 | Brazil | This study |
VWS | truncation | 1219 | del T | Ser407LeufsX28 | 9 | Brazil | This study |
NS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | This study |
NS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | This study |
PPS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | This study |
PPS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | Brazil | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | Brazil | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | Brazil | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | Brazil | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | Brazil | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | NS | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | NS | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | This study |
VWS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | 14 |
VWS | truncation | 1234 | C>T | Arg412X | 9 | N Eur | This study |
VWS | missense | 1262 | T>G | Leu421Arg | 9 | N Eur | This study |
VWS | truncation | 1264 | C>T | Gln422X | 9 | Brazil | This study |
VWS | missense | 1268 | T>C | Ile423Thr | 9 | NS | This study |
PPS | missense | 1288 | G>A | Asp430Asn | 9 | N Eur | 14 |
PPS | truncation | 1291_1311 | del/ins GTAGAGGCTAAACTCCCTGGAA | Asn431ValfsX70 | 9 | N Eur | This study |
VWS | missense | 1296_97 | delins TT | Val433Phe | 9 | Germany | This study |
VWS | truncation | 1303_1307 | del | Gln435GlufsX64 | 9 | Brazil | This study |
VWS | truncation | 1327 | del C | Leu443PhefsX46 | 9 | N Eur | This study |
VWS | truncation | 1357_1368 | del | QPTP Gln453fsX43 | 9 | N Eur | This study |
VWS | truncation | 1368 | dup C | Ser457GlnfsX43 | 9 | N Eur | This study |
VWS | truncation | 1369_1370 | ins TGCAGCCCAT | Ser457MetfsX27 | 9 | N Eur | This study |
VWS | truncation | 1372 | dup A | Met458AsnfsX43 | 9 | Brazil | This study |
VWS | truncation | 1385 | del C | Pro462LeufsX27 | 9 | Brazil | This study |
VWS | truncation | 1385 | dup C | Pro462fsX39 | 9 | N Eur | 14 |
VWS | truncation | 1386_1387 | ins C | Pro462_Ala463ArgfsX38 | 9 | N Eur | This study |
NS | splicing | -2 | A>G (100%>0%) | p.? | IVS2 | NS | This study |
VWS | splicing | -2 | A>G (100%>0%) | p.? | IVS2 | Brazil | This study |
VWS | splicing | -2 | A>G (100%>0%) | p.? | IVS2 | Brazil | This study |
VWS | splicing | -1 | G>A (100%>0%) | p.? | IVS3 | Brazil | This study |
VWS | splicing | -1 | G>T (100%>0%) | p.? | IVS3 | N Eur | This study |
PPS | splicing | 1 | G>T (100%>0%) | Val18_Lys58del | IVS3 | Belgium | This study |
VWS | splicing | 1 | G>A (100%>0%) | Val18_Lys58del | IVS3 | Belgium | This study |
PPS | splicing | 3 | A>C (71%>2%) | Val18_Lys58del | IVS3 | N Eur | This study |
VWS | splicing | -5 | T>G (22%>5%) | p.? | IVS6 | Brazil | This study |
VWS | splicing | -1 | G>A (100%>0%) | p.? | IVS6 | Brazil | This study |
VWS | splicing | -3 | C>G (55%>1%) | p.? | IVS7 | Brazil | This study |
VWS | splicing | -2 | A>G (100%>0%) | p.? | IVS7 | Brazil | This study |
In six cases, the phenotype was not specified (NS). Table does not include six cases with microdeletions of IRF6 (see text).
Nucleotide (nt) counted from start codon if mutation is located in an exon or counted from nearest exon if located in an intron. Reference sequences for cDNA and genomic DNA were NM_006147.2 and RP3-434o14 (Genbank AL022398), respectively.
All protein and exon splicing changes are deduced and not experimentally verified. Reference protein sequence is NP_006138. Frameshift mutations (fs) are predicted to add the indicated number of amino acids beyond the mutation (fsXnumber). Residues located in the DNA binding domain (yellow) or protein binding domain (green) are indicated. For splicing mutations, the values represent the change in probability of finding the indicated nucleotide at a splice junction (Zhang et al., 1998). Predicted protein for splicing mutation is based on computational analysis shown in Figure 3.
Exon and intron (IVS) numbering are based on ENSG00000117595 (www.ensembl.org).
Geographic origins of pedigrees include the indicated countries, or Northern Europe (N Eur) if proband is white, but country is not known or origins not specified (NS).