De novo mutations identified in NTD-affected trios and confirmed by Sanger sequencing.
| Family | NTD type | Chr | Position | Genes | cDNA change | Amino acid change | Polyphen HDIV* |
|---|---|---|---|---|---|---|---|
| Loss-of-function de novo mutations (nonsense, frameshift, splicing) | |||||||
| Pr394 | MMC | 4 | 77 662 169 | SHROOM3 | c.2843_2844insG | p.L948fs | NA |
| PrZRV | Anen | 4 | 77 660 502 | SHROOM3 | c.1176C>G | p.Y392X | NA |
| Pr134 | MMC | 2 | 223 161 800 | PAX3 | c.218C>A | p.S73X | NA |
| Pr201 | MMC | 15 | 44 116 692 | MFAP1 | c.69del7 | p.K23fs | NA |
| Pr389 | MMC | X | 41 202 544 | DDX3X | c.620dupA | p.Q207fs | NA |
| PrYPT | MMC | 7 | 73 279 630 | WBSCR28 | c.380G>A | p.W127X | NA |
| Missense and synonymous de novo mutations | |||||||
| Pr548 | MMC | 1 | 24 668 728 | GRHL3 | c.1171C>T | p.R391C | 1 |
| Pr548 | MMC | 19 | 39 798 985 | LRFN1 | c.1604C>T | p.T535I | 1 |
| Pr548 | MMC | 9 | 124 751 686 | TTLL11 | c.1327A>G | p.N443D | 0.968 |
| Pr125 | MMC | 19 | 5 214 591 | PTPRS† | c.4475G>A | p.R1049Q | 0.998 |
| Pr125 | MMC | 2 | 27 435 209 | ATRAID | c.138G>A | p.A46A | NA |
| Pr122 | MMC | 12 | 123 341 629 | HIP1R | c.1682G>T | p.G561V | 0.019 |
| Pr122 | MMC | 17 | 71 232 301 | C17orf80 | c.1441C>T | p.R481W | 0.099 |
| Pr122 | MMC | X | 53 592 096 | HUWE1 | c.6812G>A | p.S2271N | 0 |
| Pr134 | MMC | 14 | 105 179 874 | INF2† | c.2971C>T | p.R991W | 1 |
| Pr191 | MMC | 8 | 10 464 772 | RP1L1† | c.6836C>T | p.P2279L | 0.053 |
| Pr191 | MMC | 20 | 62 371 335 | SLC2A4RG | c.70C>T | p.R24C | 0.426 |
| Pr20 | MMC | 3 | 38 317 786 | SLC22A13 | c.1246G>A | p.V416M | 0.948 |
| Pr20 | MMC | 16 | 31 383 022 | ITGAX | c.2077C>G | p.Q693E | 0.001 |
| Pr201 | MMC | 2 | 47 703 654 | MSH2† | c.1956A>G | p.Q652Q | NA |
| Pr202 | MMC | 6 | 30 122 164 | TRIM10 | c.1028A>T | p.D343V | 1 |
| Pr202 | MMC | 7 | 23 775 208 | STK31 | c.535A>C | p.I179L | 0.039 |
| Pr25 | MMC | 9 | 134 183 554 | PPAPDC3† | c.696C>T | p.I232I | NA |
| Pr263 | MMC | 6 | 1 390 351 | FOXF2 | c.169G>A | p.A57T | 0.01 |
| Pr28 | MMC | 8 | 124 333 387 | ATAD2 | c.4160G>A | p.S1387N | 0.001 |
| Pr282 | MMC | 19 | 808 439 | PTBP1 | c.1233C>A | p.N411K | 0.013 |
| Pr389 | MMC | 7 | 100 285 176 | GIGYF1 | c.325C>T | p.P109S | 0.728 |
| Pr402 | MMC | 17 | 19 319 353 | RNF112 | c.1761C>T | p.A587A | NA |
| Pr402 | MMC | 3 | 49 775 724 | IP6K1 | c.355C>T | p.R119C | 1 |
| Pr402 | MMC | 4 | 48 424 093 | SLAIN2 | c.1745G>C | p.X582S | NA |
| Pr530 | MMC | 3 | 57 616 163 | DENND6A | c.1605A>C | p.E535D | 0.997 |
| Pr551 | MMC | 9 | 130 279 261 | FAM129B | c. 848C>T | p.A283V | 0.004 |
| Pr553 | MMC | 19 | 39 329 153 | HNRNPL | c.1441C>T | p.R481W | 1 |
| Pr554 | Anen | 3 | 142 741 447 | U2SURP | c.961G>A | p.G321S | 1 |
| Pr554 | Anen | 5 | 93 966 388 | ANKRD32 | c.371T>C | p.F124S | 0.999 |
| Pr67 | MMC | 2 | 44 566 318 | PREPL | c.937C>G | p.L313V | 1 |
| Pr67 | MMC | 5 | 176 314 262 | HK3 | c.1677G>A | p.V559V | NA |
| Pr67 | MMC | 9 | 33 264 606 | BAG1 | c.67G>A | p.A23T | 0.897 |
| PrKKS | MMC | 15 | 43 621 819 | LCMT2† | c.869T>C | p.I290T | 0.201 |
| PrKKS | MMC | 7 | 11 076 097 | PHF14 | c.1655G>C | p.R552P | 0.998 |
| PrTVB | MMC | 22 | 41 558 745 | EP300† | c.3690A>G | p.Q1230Q | NA |
| PrVWA | MMC | 9 | 120 475 791 | TLR4 | c.1385C>T | p.A462V | 0.006 |
*Probably damaging (polyphen HDIV ≥0.957), possibly damaging (0.453 ≤ polyphen HDIV ≤0.956); benign (polyphen HDIV ≤0.452).
†Mutation previously reported in the ExAC database (http://exac.broadinstitute.org/). Reported mutations frequencies are PTPRS (frequency: 0.000008368); INF2 (frequency: 0.000009451); RP1L1 (frequency: 0.0001411); MSH2 (frequency: 0.0001730), PPAPDC3 (frequency: 00003366); LCMT2 (frequency: 0.000008281); EP300 (frequency: 0.0000082).
Anen, anencephaly; MMC, myelomeningocele; NA, non-applicable; NTD, neural tube defect.