Table 1.
Synthesis of the clinical and genetic features of the nine patients carrying IFIH1 variants.
| PATIENT 1 | PATIENT 2 | PATIENT 3 | PATIENT 4 | PATIENT 5 | PATIENT 6 | PATIENT 7 | PATIENT 8 | |
|---|---|---|---|---|---|---|---|---|
| CLINICAL FEATURES | ||||||||
| Sex | F | M | F | M | F | F | M | M |
| Origin | Moroccan | Romanian | Hungarian | Albanese | Caucasian/Peruvian | Colombian/El Salvadorian | Caucasian | Caucasian |
| Intestinal phenotype * | IME | CD (A1a,L3,B1,G1)* | CD (A1a,L3,B1,G1)* | IBDU, colonic NLH | UC (E4,S1)* | UC (E4,S1)* | CD (A1bL3B1G 1)* | CD (A1a,L2,B 1,G1)* |
| Age at onset | 20 days | 6 months | 2 years | 3 months | 3 years | 1.5 years | 6 years | 2 years |
| Age at diagnosis | 2 months | 1 year | 2 years | 8 months | 4 years | 2 years | 6 years | 4 years |
| Infection(s) prior to IBD onset | + (CMV) | + (CMV) | - | - | - | - | - | - |
| Recurrent/severe infections | + | - | - | - | - | - | - | - |
| Other immune-mediated diseases | - | - | - | - | PSC | - | AIH, JIA, Psoriasis | - |
| Family history of IBD | - | - | - | - | + | - | - | + |
| IFIH1 COMPLETE LoF VARIANTS | ||||||||
| Zygosity | Homo | Het | Het | Het | Het | Het | Het | Het |
| Inheritance | P,M-both unaffected | P-unaffected | M-unaffected | M-unaffected | P-affected | P-unaffected | P-unaffected | P-unaffected |
| Nucleotide change | c.2016delA | c.2035_2036delTT | c.2807+1G>A | c.688C>T | c.1879G>T | c.1879G>T | c.2807+1G>A | c.2035_2036delTT |
| Amino acid change | p.Asp673IlefsTer5 | p.Leu679IlefsTer3 | Skipping of exon 14 | p.Gln230Ter | p.Glu627Ter | p.Glu627Ter | Skipping of exon 11 | p.Leu679IlefsTe r3 |
| gnomAD frequency § | 2.99e-4 | 1.06e-4 | 6.34e-3 | 2.79e-5 | 3.19e-3 | 3.19e-3 | 6.34e-3 | 1.06e-4 |
| CADD; MSC-CADD Impact Pred | NA | NA | 24; high | 37; high | 40; high | 40; high | 24; high | NA |
| HYPOMORPHIC AND NORMALLY FUNCTIONING IFIH1 VARIANTS | ||||||||
| Zygosity | - | Het | Het | - | - | Het | Het | Het |
| Inheritance | - | M-unaffected | 'P-unaffected | - | - | M-unaffected | P-unaffected | P-unaffected |
| Nucleotide change | - | c.1694G>T | c.2105C>T | - | - | c.C373A | c.C2105T | c.A1909G |
| Amino acid change | - | p.Cys565Phe | p.Thr702Ile | - | - | p.Leu125Met | p.Thr702Ile | p.Lys637Glu |
| gnomAD frequency § | - | 5.45e-5 | 2.34e-3 | - | - | 1.99e-5 | 2.34e-3 | 1.2e-5 |
| Protein function | - | Hypomorphic | Normal functioning | - | - | Hypomorphic | Normal functioning | Hypo morphic |
| CADD; MSC-CADD Impact Pred | - | 19; high | 10; low | - | - | 20; high | 10; low | 22; high |
* IBD phenotype according to the Paris Classification of Pediatric IBDs (Levine et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification. Inflamm Bowel Dis 2011; 17(6):1314–21).
The gnomAD frequency is taken from gnomAD v2.1.1.
AIH: autoimmune hepatitis. CD: Crohn’s disease. CMV: Cytomegalovirus. IBDU: Undetermined Inflammatory Bowel Disease. IME: immune-mediated enteropathy. JIA: juvenile idiopathic arthritis. NLH: nodular lymphatic hyperplasia PSC: primary sclerosing cholangitis. UC: ulcerative colitis. URI: Upper Respiratory Infection.
LoF: loss-of-function. Hom: Homozygous. Het: Heterozygous. P: paternal. M: maternal. NA: not available.