Table 3.
Summary of pathogenic and likely pathogenic variants identified in the cohort
| Known Genes | |||||||||||
| CaseID | Limb presentations | Systemic features | Family history | No. of affected limbs | Locus | Zygosity | cDNA change | Protein change | ACMG grade | Reference (PMID) | |
| DISCO-JST1 | reduction anomaly | Y | Y | B-H | SALL4 | Het | c.1823del | p.Asn608Thrfs∗2 | P | this study | |
| DISCO-JST8 | reduction anomaly | Y | N | B-H, B-F | SLC26A2 | NAa | c.136_137insTT | p.Asp46Valfs∗44 | P | this study | |
| DISCO-JST13 | syndactyly | Y | N | B-H, B-F | FGFR2 | Het | c.758C > G | p.Pro253Arg | P | 7719344 | |
| DISCO-JST17 | brachydactyly | N | Y | B-H | GDF5 | Het | c.932T > C | p.Leu311Pro | LP | this study | |
| DISCO-JST22 | syndactyly | Y | Y | B-H, L-F | GJA1 | Het | c.119C > T | p.Ala40Val | P | 25327171 and 15879313 | |
| DISCO-JST28 | polydactyly | Y | N | B-H, B-F | GLI3 | Het | c.1474del | p.Asp492Thrfs∗10 | P | this study | |
| DISCO-JST29 | reduction anomaly | Y | N | B-H | FANCA | Hemi | c.3537+2T > C | p.? | P | this study | |
| DISCO-JST33 | synpolydactyly | N | Y | R-H | HOXD13 | Het | c.917G > A | p.Arg306Gln | P | 22374128 and 24789103 | |
| DISCO-JST39 | syndactyly | Y | N | B-H, B-F | FGFR2 | Het | c.758C > G | p.Pro253Arg | P | 7719344 | |
| DISCO-JST41 | reduction anomaly | Y | Y | B-H | SALL4 | Het | c.595del | p.Asp199Metfs∗41 | P | this study | |
| DISCO-JST47 | reduction anomaly | Y | Y | B-H | SALL4 | Het | c.2462-1G > T | p.? | P | this study | |
| DISCO-JST48 | syndactyly | Y | N | B-H, B-F | FGFR2; RYR1 | Het; Het | c.755C > G;c.12788_12793dup | p.Ser252Trp; p.Glu4263_Gly4264dup | P; VOUS | 7719344; this study | |
| DISCO-JST51 | syndactyly | Y | N | B-H, B-F | FGFR2 | Het | c.758C > G | p.Pro253Arg | P | 7719344 | |
| DISCO-JST57 | syndactyly | N | Y | R-H | HOXD13 | Het | c.183_203dup | p.Ala65_Ala71dup | P | this study | |
| DISCO-JST70 | syndactyly | N | N | B-H, B-F | GLI3 | Het | c.480del | p.Ala161Profs∗55 | P | this study | |
| DISCO-JST72 | reduction anomaly | Y | Y | R-H | SALL4 | Het | c.1746_1747delinsTGTGGG | p.Lys582Asnfs∗17 | P | this study | |
| DISCO-JST74 | broad thumbs | Y | N | R-H | CREBBP | Het | c.4471C > T | p.Gln1491∗ | P | this study | |
| Novel candidate genes | |||||||||||
| CaseID | Limb presentations | Systemic features | Family history | Affected site | Locus | Zygosity | cDNA change | Protein change | gnomAD MAF | ||
| DISCO-JST24 | reduction anomaly | Y | N | B-H | RPL9 | Het | c.-2+2T > A | p.? | 0 | ||
| DISCO-JST19 | syndactyly | N | N | R-H | UBA2 | Het | c.811A > T | p.Lys271Ter | 0 | ||
| Structural variants | |||||||||||
| Case ID | Limb presentations | Systemic features | Family history | Affected site | Locus | Zygosity | Dosage | ||||
| DISCO-JST9 | polydactyly | Y | N | R-H | 6q25-6q27 | Het | deletion | ||||
| DISCO-JST23 | polydactyly | N | Y | B-H | 7q36.3 | Het | duplication | ||||
| DISCO-JST29 | reduction anomaly | Y | N | B-H | 16q24.3 | Het | deletion | ||||
| VOUS | |||||||||||
| CaseID | Limb presentations | Systemic features | Family history | Affected site | Locus | Zygosity | cDNA change | Protein change | gnomAD MAF | ||
| DISCO-JST35 | syndactyly | N | N | L-H | GLI3 | Het | c.103G > A | p.Ala35Thr | 0 | ||
| DISCO-JST38 | polydactyly | Y | N | R-H | FANCB | Het | c.2166-8delT | p.? | 0 | ||
| DISCO-JST55 | syndactyly | N | N | R-H | GLI3 | Het | c.3415G > T | p.Ala1139Ser | 4.01E-06 | ||
| DISCO-JST8 | reduction anomaly | Y | N | B-H, B-F | SLC26A2 | NAa | c.1512G > A | p.Met504Ile | 2.76E-4 | ||
Y, yes or present; N, not present; No, number; H, hand; F, foot; Het, heterozygous; B, bilateral; R, right; L, left; Hom, homozygous; P, pathogenic; LP, likely pathogenic; VOUS, variant of unknown significance; MAF, minor allele frequency; NA, not available.
a
Due to lack of maternal sample, the zygosity cannot be determined.