TTC7A mutation must be considered in patients with repeated intestinal atresia associated with early inflammatory bowel disease: Two new case reports and a literature review

TTC7A: Steward of Intestinal Health

“…Furthermore, tissue analysis of resected duodenal atretic areas showed ulcerations in the mucosa, loss of epithelial polarity, mucosal sloughing, apoptotic bodies, and loss of villi architecture, which were commonly reported features in patient histology 15 . Along with MIA, patients showed other intestinal defects, including meconium peritonitis, omphalocele, and bowel distension 1, 7, 15…”

“…Superscript numbers in Patient column refer to reference citations.ARDS, acute respiratory distress syndrome; c, complementary DNA location; CVID, common variable immune deficiency; Het, compound heterozygous mutation; Hom, homozygous mutation; p. protein or amino acid location.aNational Center for Biotechnology Information reference sequences for TTC7A were absent or varied between publications. Among the 15 reports citing TTC7A-deficiency patients, 63, 5, 6, 8, 9, 15 referenced mutations with NM_020458.3 (transcript variant 2, coding sequence from 369 to 2945 nucleotides) and NP_065191.2 (isoform 2, 858 amino acids). Lien et al 11 and Neves et al 13 reported mutations based on NM_001288951.1 (transcript variant 1, coding sequence from 369 to 3017 nucleotides) and NP_001275880.1 (isoform 1, 882 amino acids).…”

“…TTC7A-deficiency patients have been reported to have widespread atresias affecting the pylorus, small bowel, appendix, ileocecal valve, colon, and anal regions 1, 2, 3, 5, 7, 9, 13, 14. In 2 cases in which substantial resections were performed early, a detailed analysis of the resected tissues showed that the lumen was strictured or completely lost, intestinal layers showed fibrosis, calcified fibrotic areas, reduced lymphoid follicle size, and a thickened bowel wall suggestive of chronic intestinal inflammation 15 . Furthermore, tissue analysis of resected duodenal atretic areas showed ulcerations in the mucosa, loss of epithelial polarity, mucosal sloughing, apoptotic bodies, and loss of villi architecture, which were commonly reported features in patient histology 15 .…”

“…In 2 cases in which substantial resections were performed early, a detailed analysis of the resected tissues showed that the lumen was strictured or completely lost, intestinal layers showed fibrosis, calcified fibrotic areas, reduced lymphoid follicle size, and a thickened bowel wall suggestive of chronic intestinal inflammation 15 . Furthermore, tissue analysis of resected duodenal atretic areas showed ulcerations in the mucosa, loss of epithelial polarity, mucosal sloughing, apoptotic bodies, and loss of villi architecture, which were commonly reported features in patient histology 15 . Along with MIA, patients showed other intestinal defects, including meconium peritonitis, omphalocele, and bowel distension 1, 7, 15…”

“…Rare autosomal-recessive variants in tetratricopeptide repeat domain 7A ( TTC7A ) have been discovered in patients presenting with severe intestinal and immune diseases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. Mounting evidence has indicated that TTC7A mutations can result in various phenotypes that may or may not be associated with combined immunodeficiency (CID), including multiple intestinal atresias (MIA) and very early onset inflammatory bowel disease (VEOIBD), a form of IBD in children younger than 6 years of age 3, 5, 13.…”