List of all causative/possibly causative mutations identified in our cohort
| Patient ID | Sex | Gene | Mutation | Inheritance | Mode of inheritance | Degree of ID | Consistency with classic phenotype | See online supplementary figure # |
|---|---|---|---|---|---|---|---|---|
| Certainly-causative mutations | ||||||||
| APN-58 | M | DYRK1A | chr21:g.38858865C>T; c.613C>T; p.Arg205*; htz | De novo | AD | ++ | Yes | S2 |
| APN-87 | M | DYRKA1 | chr21:g.38858873del; c.621_624delinsGAA; p.Glu208Asnfs*3; htz | De novo | AD | ++ | Yes | S2 |
| APN-63 | M | GRIN1 | chr9:g.140056661C>G; c.1733C>G; p.Pro578Arg; htz | De novo | AD | +++ | Yes | S3 |
| APN-14 | M | MED13L | chr12:g.116406845_116406852del; c.6118_6125del; p.Gly2040Asnfs*32; htz | De novo | AD | ++ | Partially | S4 |
| APN-46 | M | RAI1 | chr17:g.17698594_17698598del; c.2332_2336del; p.Gly778Glnfs*7; htz | De novo | AD | ++ | Partially | S5 |
| APN-122 | F | SHANK3 | chr:g.51159168_51159183dup; c.2955_2970dup; p.Pro992Argfs*325; htz | De novo | AD | +++ | Yes | S6 |
| APN-38 | M | SLC2A1 | chr1:g.43395407G>A; c.724C>T; p.Gln242*; htz | De novo | AD | +++ | Yes | S7 |
| APN-139 | M | SYNGAP1 | chr6:g.33414346G>A; c.3583-6G>A; p.Val1195Alafs*27; htz; splice | De novo | AD | ++ | Yes | S8 |
| APN-41 | M | TCF4 | chr18:g.53017622_53017625del; c.514_517del; p.Lys172Phefs*61; htz | De novo | AD | +++ | Yes | S9 |
| APN-117 | F | TCF4 | chr18:g.53017619G>A; c.520C>T; p.Arg174*; htz | De novo | AD | ++ | No | S9 |
| APN-138 | M | ATRX | chrX: g.76972632G>A; c.109C>T; p.Arg37* (rs122445108); hemz | Inherited (Ma) | XL | +++ | Yes | S10 |
| APN-137 | M | CUL4B | chrX: g.119681009_119681010del; c.811_812del; p.Gln271Aspfs*11; hemz | Inherited (Ma) | XL | +++ | Partially | S11 |
| APN-42 | M | DMD | chrX:g.31164440del; c.10889del; p.Arg3630Glnfs*27; hemz | Inherited (Ma) | XL | ++ | No | S12 |
| APN-26 | M | FMR1 | Last exon deletion; hemz | Inherited (Ma)* | XL | +++ | Partially | S13 |
| APN-113 | M | HCFC1; (ATRX) | chrX:g.153230153G>A; c.218C>T; p.Ala73Val; hemz; (chrX:g.76939735G>C, c.1013C>G, p.Ser338Cys; hemz) | Inherited (Ma) Inherited (Ma) | XL; (XL) | +++ | Yes (partially) | 3 |
| APN-82 | M | IL1RAPL1 | chrX:g.29935696_29935705del; c.894_903del; p.Trp299Thrfs*18; hemz | Inherited (Ma) | XL | ++ | Yes | S14 |
| APN-68 | M | IQSEC2 | chrX:g.53268395G>A; c.3097C>T; p.Gln1033*; hemz | De novo | XL | +++ | Yes | S15 |
| APN-34 | M | KDM5C | chrX:g.53228250C>G; c.2152G>C; p.Ala718Pro; hemz | De novo | XL | ++ | Partially | S16 |
| APN-135 | M | KDM5C | chrX:g.53240784dup; c.1296dup; p.Glu433*; hemz | Inherited (Ma) | XL | ++ | Partially | S16 |
| APN-16 | M | MAOA | chrX:g.43590942_43590943delinsTT; c.797_798delinsTT; p.Cys266Phe; hemz | Inherited (Ma) | XL | +/− | Yes | 42 |
| APN-130 | F | MECP2 | chrX: g.153296363G>A; c.916C>T; p.Arg306Cys (rs28935468); htz | De novo | XL | +++ | Partially | S17 |
| APN-142 | F | MECP2 | chrX:g.153296777G>A; c.502C>T; p.Arg168* (rs61748421); htz | De novo | XL | +++ | Partially | S17 |
| APN-3 | M | MECP2 | Complex rearrangement of exon 4; hemz | Inherited (Ma) | XL | +++ | Yes | S17 |
| APN-105 | M | PHF8; (DOCK8) | chrX:g.54028583C>G; c.1249+5G>C; p.Tyr406Phefs*24; hemz; (chr9:g.407035G>T; c.3496G>T; p.Glu1166*; htz) | Inherited (Ma); (de novo) | XL; (AD) | + | Partially (No) | S18 |
| APN-43 | M | SLC9A6 | chrX:g.135080258_135080262del; c.526-9_526-5del; p.?; splice disrupted; hemz | Inherited (Ma) | XL | + | Yes | Masurel-Paulet et al, in preparation |
| APN-110 | M | SLC16A2 | chrX:g.73749067T>C; c.1412T>C ; p.Leu471Pro (rs122455132); hemz | Inherited (Ma) | XL | +++ | Yes | S19 |
| Possibly causative mutations | ||||||||
| APN-131 | M | SLC2A1; (ANKRD11) | chr1:g.43392779del; c.1412delG; p.Gly471Glufs*37; htz; (chr16:g.89348867G>T; c.4083C>A; p.His1361Gln; htz) | Inherited (Pa); Inherited (Ma) | AD; AD | +++ | Partially | S7 |
| APN-101 | M | TCF4 | chr18:g.52899907C>T; c.1487-5G>A; p.Arg495_Gly496insAla?,; htz | De novo ? † | AD | ++ | No | S9 |
| APN-99 | M | NLGN3 | chrX:g.70389249C>T; c.1849C>T; p.Arg617Trp; hemz | Inherited (Ma) | XL | +++ | Yes | S20 |
| APN-70 | M | PQBP1 | chrX:g.48760294C>T; c.731C>T; p.Pro244Leu; hemz | Inherited (Ma) | XL | ++ | No | S21 |
*Present in the three brothers. Mother untested, but most probably maternally inherited.
†Absent from the mother, deceased father (untested).
In bold: mutations previously reported in other patients.
–: no ID, +: mild ID, ++: moderate ID, +++: severe ID.
AD, autosomal dominant; F, female; hemz, hemizygous; htz, heterozygous; ID, intellectual disability; M, male; Ma, maternally-inherited; MAOA, Monoamine Oxidase A enzyme; Pa, paternally inherited; XL, X-linked.