Table 1.
Clinical characterization of male patients with non-synonymous NOX1 hemizygous variants.
| Patient ID |
NOX1 variants |
Gen der |
Age of diagnosis (of symptoms) in years |
Diagnosis Paris class.62 |
Family history for IBD |
Intestinal and extra-intestinal symptoms/findings on examination (age in years) |
Histology | Treatment for IBD |
|---|---|---|---|---|---|---|---|---|
|
| ||||||||
| P1 | c.A364C p.N122H | M | 5 (2) | IBDU; E4 | Negative | Presented with bloody stools and failure to thrive (2), progression from proctitis (5) to pancolitis (19), terminal ileum normal, perianal skin tags; EBV-associated HLH (14) whilst on AZA | Cryptits, crypt architectural distortion, crypt abscesses, focal Paneth cell metaplasia, single micro-granuloma. | Oral CS, ASA, AZA, MTX, ADA |
|
| ||||||||
| P2 | c.T1408C p.Y470H | M | 9.7 | CD; L3L4a, B1 | Negative | Initially presented with weight loss and rectal bleeding | Granulomata, neutrophilic infiltration into crypts and surface epithelium | Oral CS, IFX, MTX |
|
| ||||||||
| P3 | c.C201G p.I67M | M | 8.6 (7.8) | UC; E4 | Mother (UC) | Presented with abdominal pain and alternating formed stool/diarrhea with blood/mucous (7.8). At diagnosis microscopic pancolitis (8.6), later macroscopic disease in rectosigmoid (17.5); No EIMs | Neutrophil infiltrate, (peri-) cryptitis, branching and focal dropout of glands, regeneration. No granuloma. | 5-ASA |
|
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| P4 | c.G860A p.R287Q | M | 9.9 (9.5) | CD; L3L4a, B1p | Brother and aunt (CD) | Presented with abdominal pain and loose stools (9.9); right colon and ileal disease distribution (13); Perianal skin tags and fistula (15.8) | Granulomata, focal branching, (peri-) cryptitis, intraepithelial lymphocytes, lymphoplasmacytic infiltrate, basal cell hyperplasia | 5-ASA, SALZ, AB |
|
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| P5 | c.G860A p.R287Q | M | 10.5 (8.5) | CD; L3L4ab; B2p | Brother and aunt (CD) | Presented with long standing abdominal pain, variably loose stools/constipation (8.5), and more recent periodic blood PR (10.3). Diagnostic scope primarily small bowel disease and minor colonic involvement; perianal fistula (10.5). | Cryptitis, pericryptitis, crypt distortion, cell infiltrate, giant cells. No granulomas. | 5-ASA, AB, IFX, CS, NUT, ADA. |
| Ileocecal resection for stricture (12.8); second ileocecal resection (15.6) | ||||||||
|
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| P6 | c.G860A p.R287Q | M | 5.7 (5.3) | UC; E2 | cousins (CD or UC) | Presented with rectal bleeding (5.3). At scope, diagnosed with left sided colitis (5.7). No GI Sx since age 9yo. At 15yo, diagnosed with Stage IVB non-bulk nodular sclerosing Hodgkin’s disease. In remission following therapy. | Chronic inflammatory infiltrate | Previously SALZ. Currently on no therapy. |
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| P7 | c. A878G p.Q293R | M | 9.7 (9.4) | CD; L2L4a | Negative | Presented with bloody diarrhea, arthralgia, lethargy, and weight loss (9.4). Pancolitis at diagnosis (9.7), upper GI inflammation (17.5); arthralgias | Cryptitis, crypt abscesses, Paneth cell metaplasia, apoptotic epithelial cells involving most colonic crypts, transepithelial inflammation, No granulomas. | AB, IV and oral CS, SALZ, MTX, IFX |
|
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| P8 | c.A1489G p.T497A | M | 7.1 (7.0) | UC; E4 | Negative | Bloody diarrhea (7.0); diagnosed with pancolitis (7.1). Single episode of pancreatitis (13.3). In clinical remission since age 13.3. | Focal cryptitis, crypt abscesses, moderate architectural distortion, paneth cell metaplasia, | 5-ASA, SALZ, CS. |
Abbreviations: AB, oral or intravenous antibiotics given for treatment of colitis, bowel decontamination, and fistula treatment; ADA, adalimumab; 5-ASA, 5-aminosalicylic acid; AZA, azathioprine; CD, Crohn’s disease; CS, corticosteroids; EBV, Epstein–Barr virus; EIMs, extra-intestinal manifestations; F, female; HLH, hemophagocytic lymphohistiocytosis; IBDU, IBD unclassified; IFX, infliximab; M, male; MTX, methotrexate; NUT, polymeric/elemental diet; PR, per rectum; SALZ, sulfasalazine; UC, ulcerative colitis.