Table 2.
Categories, function and phenotype overview of identified high-confidence candidate genes
| Gene | No. pats. | Variant level classificatione | Gene level classification [No. of cat.]c | Combined score [1–4] | Main pathwayd | Phenotype | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| V | IV | III | Heigth [SDS ± s] | OFC [SDS ± s] | Syndromic | Common features (no. of individuals) | |||||
| CPZ | 3a | 3 | 1 | 3 | −3.6 ± 1.4 | −2.3 ± 1 | 0/3 | Short neck (2/3), hypertelorism (2/3), low set ears (3/3), wide intermammillary distance (2/3) | |||
| EDEM3 | 2 | 2 | 3 | 3 | Protein processing | −2 ± 0.1 | −1.7 ± 0.7 | 0/3 | High arched eye brows (2/2), thin upper lip (2/2) | ||
| FBRS | 3a | 2 | 1 | 3 | 3 | −2.2 ± −0.2 | −2 ± 0.4 | 0/3 | Thin hair (2/3), prominent ears (2/3), thin lips (2/3), brachydactyly (2/3) | ||
| IFT81 | 2 | 2 | 2 | 3 | Cilium Assembly | −2.9 ± 0 | −3.1 ± 1 | 0/3 | wide nasal bridge (2/2), high arched eye brows (2/2) | ||
| KCND1 | 2 | 2 | 1 | 3 | Cardiac conduction | −2.9 ± 0.4 | −2.4 ± 1.1 | 0/2 | Fair hair (2/2), sparse eye brows (2/2), thin lips (2/2), brachydactyly (2/2) | ||
| LAMA5 | 8b | 4 | 4 | 4 | 3 | Human papillomavirus infection | −2.9 ± 0.6 | −1.4 ± 1.1 | 2/8 | Thin lips (4/8), barrel chest (5/8), sandal gap (6/8) | |
| MED24 | 2 | 1 | 1 | 5 | 4 | Thyroid hormone signaling | −2.5 ± 0.4 | −1.5 ± 0.3 | 0/2 | Thin lips (2/2), brachydactyly (2/2) | |
| PLXNA3 | 2 | 2 | 5 | 3 | Axon guidance | −2 ± 0.3 | −0.8 ± 1 | 0/2 | Lateral hypoplasia of brows (2/2), broad thumbs (2/2) | ||
| RASA3 | 2 | 1 | 1 | 4 | 3–4 | Ras signaling | −2.7 ± 0.5 | −2 ± 0 | 0/2 | Broad nasal tip (2/2), thin lips (2/2), barrel chest (2/2) | |
| SLC7A8 | 2 | 2 | 3 | 3 | Protein degradation | −2.9 ± 0.7 | −2 ± 0.5 | 0/2 | Brachydactyly (2/2) | ||
| UBR4 | 6b | 5 | 1 | 4 | 2–3 | Human papillomavirus infection | −2.9 ± 0.5 | −1 ± 1.2 | 3/6 | Lateral sparse brows (4/6), barrel chest (4/6), brachydactyly (5/6) | |
| USP45 | 4 | 1 | 2 | 1 | 2 | 2–4 | DNA Repair | −2.9 ± 0.7 | −1.6 ± 1.1 | 0/4 | Brachydactyly (4/4) |
| ZFHX3 | 2 | 1 | 1 | 5 | 3–4 | Regulat.pluripotency of stem cells | −2.5 ± 0.7 | −2 ± 0 | 0/2 | Brachydactyly (2/2), thin lips (2/2), barrel chest (2/2) | |
aSegregation not available in 1 individual
bSegregation not available in 4 individuals
cmaximum of 8 gene level categories
dPathway from KEGG/Reactome with the highest frequency of selected genes with growth phenotype (see also Supplementary Table 10
eVariant level classification (Supplementary Tables 1-4): III—Variant of unknown significance, IV—likely pathogenic, V—pathogenic