TABLE 1.
Summary of variants in non-cohesin genes identified in CdLS-patients.
| Gene | Citation | Number of patients | Patient ID | Variant type | Variant coordinates | Zygosity | Variant classification | Gender | Score | Origin | Analysis performed |
| ANKRD11 (NM _013275.6) | Ansari et al., 2014 | 3 | NA | Frameshift deletion | c.6210 _6211del; p.(Lys2070Asnfs*31) | Heterozygous | Pathogenic | f | NA | De novo | Exome sequencing |
| NA | Frameshift deletion | c.2627delT; p.(Leu876Profs*6) | Heterozygous | Pathogenic | f | NA | De novo | Sanger sequencing | |||
| Decipher DDD-EDB257747 | Intragenic deletion | 60 kb intragenic deletion spanning exons 4–10 (chr16:89,351,798–89,412,086; hg19) | Heterozygous | Pathogenic | m | NA | De novo | Array-CGH | |||
| Parenti et al., 2016 | 2 | Patient A | Non-sense | c.5483C > A; p.(Ser1828*) | Mosaic (30% on blood DNA and 50% on fibroblast DNA) | Pathogenic | f | (12) | De novo | Exome sequencing | |
| Patient B | Frameshift deletion | c.2297 _2300delAGAA; p.(Lys766Argfs*10) | Heterozygous | Pathogenic | m | (10) | De novo | Exome sequencing | |||
| Aoi et al., 2019 | 2 | Patient 21 | Frameshift deletion | c.3255 _3256del; p.(Lys1086Glufs*15) | Heterozygous | Pathogenic | f | 8 | De novo | Exome sequencing | |
| Patient 43 | Non-sense | c.5434C > T; p.(Gln1812*) | Heterozygous | Pathogenic | m | 9 | De novo | Exome sequencing | |||
| Cucco et al., 2020 | 1 | Patient B | Frameshift deletion | c.3224 _3227del; p.(Glu1075Glyfs*242) | Heterozygous | Pathogenic | m | 10 | De novo | Exome sequencing | |
| Parenti et al., 2021 | 8 | Patient 2 | Frameshift deletion | c.1711 _1723del; p.(Thr571Alafs*15) | Heterozygous | Pathogenic | m | (9) | NA | Gene panel | |
| Patient 3 | Non-sense | c.1977C > A; p.(Tyr659*) | Heterozygous | Pathogenic | f | (13) | NA | Gene panel | |||
| Patient 4 | Frameshift deletion | c.2398 _2401delGAAA; p.(Glu800Asnfs*62) | Heterozygous | Likely pathogenic | f | (10) | Inherited (mother) | Gene panel | |||
| Patient 5 | Frameshift deletion | c.2408 _2412del; p.(Lys803Argfs*5) | Heterozygous | Pathogenic | f | (13) | De novo | Gene panel | |||
| Patient 6 | Non-sense | c.2692C > T; p.(Arg898*) | Heterozygous | Pathogenic | f | (11) | De novo | Gene panel | |||
| Patient 7 | Frameshift duplication | c.7356dupC; p.(Lys2453Glnfs*79) | Heterozygous | Pathogenic | f | (10) | De novo | Gene panel | |||
| Patient 9 | Frameshift deletion | c.1903 _1907del; p.(Lys635Glnfs*26) | Heterozygous | Pathogenic | m | (8) | NA | Gene panel | |||
| Patient 12 | Splicing | c.7470 + 2T > C; p.? | Heterozygous | Likely pathogenic | m | (6) | Inherited (mother) | Gene panel | |||
| BRD4 (NM _001379291.1) | Olley et al., 2018 | 2 | Patient 3049 | Missense | c.1289A > G; p.(Tyr430Cys) | Heterozygous | Pathogenic | f | (10) | De novo | Gene panel |
| Patient CDL038 | Frameshift deletion | c.1224delinsCA; p.(Glu408Aspfs*4) | Heterozygous | Pathogenic | f | (8) | De novo | Gene panel | |||
| Rentas et al., 2020 | 1 | Patient CDL-022 | Missense | c.1038G > C, p.(Lys346Asn) | Heterozygous | Uncertain significance | m | NA | Father not available. Not maternal | RNA sequencing | |
| AFF4 (NM _014423.4) | Izumi et al., 2015 | 3 | CHOPS T254S | Missense | c.761C > G; p.(Thr254Ser) | Heterozygous | Pathogenic | f | (3) | De novo | Exome sequencing |
| CHOPS T254A | Missense | c.760A > G; p.(Thr254Ala) | Heterozygous | Pathogenic | m | (7) | De novo | Exome sequencing | |||
| CHOPS R258W | Missense | c.772C > T; p.(Arg258Trp) | Heterozygous | Pathogenic | f | (6) | De novo | Exome sequencing | |||
| KMT2A (NM _001197104.2) | Yuan et al., 2015 | 1 | CdLS-3 | Non-sense | c.2233C > T; p.(Arg745*) | Heterozygous | Pathogenic | f | (13) | De novo | Exome sequencing |
| Parenti et al., 2017 | 1 | Patient 12 | Non-sense | c.8590C > T; p.(Gln2864*) | Heterozygous | Pathogenic | m | (11) | De novo | Gene panel | |
| Aoi et al., 2019 | 1 | Patient 27 | Non-sense | c.3592C > T; p.(Gln1198*) | Heterozygous | Pathogenic | m | 7 | De novo | Exome sequencing | |
| Krawczynska et al., 2019 | 1 | CdLS09 | Splicing | c.4012 + 1G > A; p.? | Mosaic (48% on buccal swab DNA, 0% on blood DNA) | Likely pathogenic | m | NA | NA | Gene panel | |
| Demir et al., 2020 | 1 | Case report | Frameshift deletion | c.3647 _3650delAAGA; p.(Lys1216Argfs*18) | Heterozygous | Pathogenic | f | (12) | De novo | Gene panel | |
| EP300 (NM _001429.4) | Woods et al., 2014 | 1 | Case report | Frameshift deletion | c.104 _107del; p.(Ser35Tyrfs*12) | Heterozygous | Pathogenic | m | (14) | De novo | Exome sequencing |
| Aoi et al., 2019 | 1 | Patient 6 | In frame deletion | c.7014 _7028del; p.(His2338 _Pro2342del) | Heterozygous | Uncertain significance | f | 9 | Unknown | Exome sequencing | |
| Cucco et al., 2020 | 1 | Patient A | Frameshift duplication | c.4408dupA; p.(Met1470Asnfs*3) | Heterozygous | Pathogenic | f | 9 | De novo | Exome sequencing | |
| SETD5 (NM _001080517.3) | Parenti et al., 2017 | 2 | Patient 2 | Frameshift deletion | c.2212 _2213delAT; p.(Met738Valfs*27) | Heterozygous | Pathogenic | m | (9) | De novo | Exome sequencing |
| Patient 3 | Intragenic deletion | 54 kb intragenic deletion spanning exons 3–19 (chr3:9,457,143-9,511,190; hg19) | Heterozygous | Pathogenic | f | NA | Father not available. Not maternal | Array-CGH | |||
| Aoi et al., 2019 | 1 | Patient 12 | Non-sense | c.1852C > T; p.(Arg618*) | Heterozygous | Pathogenic | f | 10 | De novo | Exome sequencing | |
| ARID1B (NM _001374828.1) | Yavarna et al., 2015 | 1 | NA | In frame deletion | c.372 _395del; p.(Ala125 _Ser132del) | Heterozygous | Uncertain significance | NA | NA | NA | Exome sequencing |
| Parenti et al., 2017 | 2 | Patient 5 | Non-sense | c.2902C > T; p.(Arg968*) | Heterozygous | Pathogenic | f | (12) | De novo | Exome sequencing | |
| Patient 6 | Splicing | c.3505-2A > G; p.(Lys1169Leufs*18) | Heterozygous | Pathogenic | m | (11) | De novo | Gene panel | |||
| SMARCB1 (NM _003073.5) | Parenti et al., 2017 | 1 | Patient 4 | Missense | c.971A > G; p.(Lys324Arg) | Heterozygous | Uncertain significance | f | (13) | Father not available. Not maternal | Gene panel |
| TAF1 (NM _004606.5) | O’Rawe et al., 2015 | 1 | Individual 4A | Missense | c.1454T > A; p.(Ile485Asn) | Hemizygous | Likely pathogenic | m | (12) | De novo | Exome sequencing |
| Cheng et al., 2020 | 1 | Individual 13 | Missense | c.3508C > T; p.(Arg1170Cys) | Hemizygous | Likely pathogenic | m | 10 | De novo | Exome sequencing | |
| USP7 (NM _003470.3) | Fountain et al., 2019 | 1 | Patient 8 | Intragenic deletion | 31 kb intragenic deletion including a portion of 5′UTR and intron 1 and the entire exon 1 (chr16:9,085,733-9,054,621; hg19) | Heterozygous | Likely pathogenic | f | (9) | De novo | Genome sequencing |
| DDX23 (NM _004818.3) | Burns et al., 2021 | 2 | Patient 5 | Missense | c.1625G > A; p.(Arg542His) | Heterozygous | Likely pathogenic | f | (9) | De novo | Genome sequencing |
| Patient 6 | Missense | c.1583G > A; p.(Arg528His) | Heterozygous | Likely pathogenic | f | (11) | De novo | Genome sequencing | |||
| CSNK1G1 (NM _022048.5) | Gold et al., 2020 | 1 | Individual 4 | Missense | c.419C > T; p.(Thr140Met) | Heterozygous | Likely pathogenic | m | (9) | De novo | Genome sequencing |
| ZMYND11 (NM _001370100.5) | Aoi et al., 2019 | 1 | Patient 53 | Frameshift deletion | c.1438delG; p.(Asp480Thrfs*3) | Heterozygous | Pathogenic | m | 15 | Inherited (mother mosaic) | Exome sequencing |
| MED13L (NM _015335.5) | Aoi et al., 2019 | 1 | Patient 5 | Missense | c.6485C > A; p.(Thr2162Lys) | Heterozygous | Likely pathogenic | f | 8 | De novo | Exome sequencing |
| PHIP (NM _017934.7) | Aoi et al., 2019 | 1 | Patient 56 | Missense | c.1156G > A; p.(Asp386Asn) | Heterozygous | Likely pathogenic | m | 6 | De novo | Exome sequencing |
| TAF6 (NM _001190415.2) | Yuan et al., 2015 | 1 | CdLS-4 | Missense | c.247C > T; p.(Arg83Cys) | Homozygous | Likely pathogenic | m | (11) | Parents heterozygous | Exome sequencing |
| Tuc et al., 2020 | 1 | Individual VI-8 | Missense | c.323T > C; p.(Ile108Thr) | Homozygous | Likely pathogenic | m | 4 | Parents heterozygous | Exome sequencing | |
| NAA50 (NM _025146.4) | Aoi et al., 2019 | 1 | Patient 19 | Non-sense | c.93C > G; p.(Tyr31*) | Heterozygous | Likely pathogenic | m | 12 | De novo | Exome sequencing |
| CREBBP (NM _004380.3) | Tang et al., 2019 | 1 | Patient 3 | Frameshift deletion | c.1715delG; p.(Gly572Glufs*17) | Heterozygous | Pathogenic | f | 9 | De novo | Exome sequencing |
| PDGFRB (NM _002609.4) | Yavarna et al., 2015 | 1 | NA | Missense | c.1113C > G; p.(Asn371Lys) | Heterozygous | Uncertain significance | NA | NA | NA | Exome sequencing |