Table 1.
Pathogenic variants identified in VEO-IBD patients upon screening of known IBD-associated Mendelian disorder genes.
| Gene | Position | Variant | GTs | GERP | CADD | GM | IT | ADD | Ethnicity | Phenotype |
|---|---|---|---|---|---|---|---|---|---|---|
| XIAP | X:123020176 |
ENST00000371199.7:c.963C>T ENSP00000360242:p.R222* |
Hem | 3.8 | 37 | 0 | 0 | 6 | EU | CD-like phenotype with a severe fistulizing perianal phenotype |
| SH2D1A | X:123504047 |
ENST00000371139.8:c.522A>T ENSP00000360181:p.R75* |
Hem | 2.7 | 38 | 0 | 0 | 6 | African | Acute EBV infection and liver failure |
| CYBA | 16:88712540 |
ENST00000261623.8:c.492G>A ENSP00000261623:p.S118N |
Hom | 4.5 | 25 | 1 | 0 | 5, 5* | South Asian | Granulomas and a non-stricturing, non-penetrating CD-like pathology |
| CYBB | X:37663371 |
ENST00000378588.4:c.1206G>A ENSP00000367851:p.W380* |
Hem | 5.6 | 40 | 1 | 0 | 0 | EU | CD (perianal disease), Hidradenitis suppurativa |
Each row represents a variant in a conserved site (GERP > 2), predicted damaging by in-silico tools, identified in VEO-IBD cases. Patient genotypes (GTs) are listed (Hem: hemizygous, if male; Hom: homozygous for the alternative allele). The number of gnomAD (GM) and INTERVAL (IT) samples that harbored similar variants in that gene (i.e., nonsense alleles) with the same genotype as our patients are also listed. Patient ADD refers to age at diagnosis (in years). Ethnic origin of patients as confirmed via PCA analysis (EU European descent). CADD scores in table refer to C-scaled scores. CD Crohn’s disease. All variants were functionally validated. All variants were absent from gnomAD and INTERVAL datasets, and therefore constituted novel variants herein identified
*The variant in CYBA was identified in two siblings. Genomic positions based on GRCh37.