Table 2.
Three GRHL2 Intron 1 Variants Associated with PPCD4
|
Open Chromatin/Methylation Marks |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Coordinates (hg19) | Coordinates (hg38) | HGVS | CADD Score | Family | TF Gained | TF Lost | H1ESC | NHDF-AD | NHEK |
| 102,505,274 | 101,493,046 | c.20+257delT | 6.62 | B4 | POC/Zinc finger proteins, STAT6 | EBF1 | CTCF DNase1 H3K4me1 | DNaseI H3K36me3H3K9ac | CTCF DNaseI H3K4me1 H3K9ac |
| 102,505,150 | 101,492,922 | c.20+133delA | 13.23 | B5 | GLI3, ZBTBZA | ZNF354C | DNaseI H3K4me1 H3K4me3 H3K9ac | DNaseI H3K9ac | CTCF H3K4me1 H3K9ac |
| 102,505,561 | 101,493,333 | c.20+544G>T | 10.76 | C15 C23 C26 C33 | ESRRA GLIS1 E2F3 | SP1 NRF1 MYC E2F2 AHR | CTCF DNaseI H3K4me1 | CTCF H3K4me1 | CTCF DNaseI H3K4me3 H3K9ac |
Three novel regulatory region variants in GRHL2 identified in British and Czech families. Variants were located in intron 1 of GRHL2, identified by WGS (C15, C23, C33, C26) or targeted sequencing (B4, B5). All three variants are absent from public databases (Kaviar, gnomAD, 1000G, UK10K, GoNL datasets), have high CADD scores, are predicted to gain or lose binding sites for TFs expressed in corneal endothelium, and fall in peaks for open chromatin or methylation marks associated with gene regulation for different cell lines. Abbreviations are as follows: H1ESC, human embryonic stem cells; NHDF-AD, adult dermal fibroblasts; NHEK, normal human epidermal keratinocytes; CTCF, CCCTC-binding factor; DNaseI, deoxyribonuclease I; H3K9ac, H3 lysine 9 acetylation; H3K4me, H3 lysine4 monomethylation; H3K4me3, H3 lysine 4 trimethylation; H3K36me3, H3 lysine 36 trimethylation.