Table 3.
Genes with high pLI scores (> 0.8) that are deleted or potentially disrupted by a duplication for which there is currently insufficient evidence to support a phenotypic expansion involving CDH/DE
| Gene (pLI score) | Disorder (MIM number) | Subject, CNV type | Homolog expressed in the developing mouse diaphragm?† | CDH Pathogenicity Score‡ | Other cases of CDH reported for this gene/disorder in humans |
|---|---|---|---|---|---|
| ACACA (pLI = 1) | Acetyl-CoA carboxylase deficiency (MIM: 613933) | Subject 18, Deletion | Yes | 81% | No/No |
| ATP7A (pLI = 1) | Occipital horn syndrome (MIM: 304150); Menkes disease (MIM: 309400) | Subject 19, Deletion | Yes | 82% | Yes/No§ |
| HMGB1 (pLI = 0.82) | N/A | Subject 20¶, Deletion | Yes | 81% | No/N/A |
| HNF1B (pLI = 1) | Renal cysts and diabetes syndrome (MIM: 137920) | Subject 18, Deletion | Yes | 97% | No/No |
| HSPH1 (pLI = 1) | N/A | Subject 20¶, Deletion | Yes | 72% | No/N/A |
| INTS2 (pLI = 1) | N/A | Subject 21, Deletion | Yes | 81% | No/N/A |
| MED13 (pLI =1) | Intellectual developmental disorder 61 (MIM: 618009) | Subject 21, Deletion | Yes | 72% | No/No |
| SYNRG (pLI = 0.93) | N/A | Subject 18, Deletion | Yes | 9% | No/N/A |
| PACC1 (pLI = 0.84) | N/A | Subject 22, Deletion | Yes | 23% | No/N/A |
| ARHGAP6 (pLI = 1) | N/A | Subject 27, Breakpoint of Duplication | Yes | 92% | No/N/A |
| DLC1 (pLI = 1) | N/A | Subject 28, Breakpoint of Duplication | N/D | 84% | No/N/A |
| FRMPD4 (pLI = 1) | Intellectual developmental disorder, X-linked 104 (MIM: 300983) | Subject 27, Breakpoint of Duplication | Yes | 99% | No/No |
| ILRUN (pLI = 0.85) | N/A | Subject 31, Breakpoint of Duplication | N/D | N/D | No/N/A |
| KANSL1 (pLI = 1) | Koolen-De Vries syndrome (MIM: 610443) | Subject 19, Breakpoint of Duplication | Yes | 57% | No/No |
| TENM1 (pLI = 1) | N/A | Subject 30, Breakpoint of Duplication | N/D | 57% | No/N/A |
Is the mouse orthologue expressed in the developing diaphragm at embryonic day (E)11.5, E12.5 and E16.5 based on whole-transcriptome expression profiles published by Russell et al. (Russell et al., 2012)? This pattern is not seen in ~ 20% of the genes evaluated by Russell et al.
A machine learning-generated centile score that ranks the similarity of this gene to a set of 31 known CDH gene in comparison to all RefSeq genes (Callaway et al., 2018).
Subject 19 is a female with additional phenotypes that are not typical for X-linked Menkes disease.
Previously published as Pt2 by Bartholdi et al. (Bartholdi et al., 2014).