Identification and intestinal histopathology of TTC7A-mutated patients. (A) Radiograph colonography with barium enema in P1 showing decreased diameter of the descending and sigmoid colon, dilated small intestine segments, and dilation of ascending and transverse colon. Rectum diameter was normal. (B) Histologic analysis of duodenal biopsy from P1 suggesting GVHD, including erosion and regeneration of the epithelial surface, focal villous atrophy, degeneration of glands, apoptotic content in crypts, and crypt loss accompanied by increase in lamina propria capillaries. (C) Chest radiograph of hypoplastic thymic tissue in P1. (D) Single nucleotide polymorphism–based mapping of the homozygous chromosomal intervals in P1 (red bars). Arrow indicates the chromosomal position of TTC7A locus within the homozygous interval on chromosome 2. (E) Identification and segregation analysis of the point mutation NM_020458:c.T1037C;p.L346P in the TTC7A gene of P1. Chromatograms display the mutation-containing TTC7A sequence in healthy heterozygous parents, 1 representative heterozygous sibling, and P1 who is homozygous for the mutation. All living siblings of P1 were heterozygous for the identified mutation. (F) Chest radiograph of P2 without visible thymic tissue. (G) Intestinal atresia included distal jejunum and the ligament of Treitz and spanned the entire distal colon. Radiographic colonography of P2 showing a small diameter of the pylorus with low passage of contrast agent. Distal intestine ends in a stoma after surgical excision of atretic tissue with no visible lumen in small bowel and colon. (H) Polymerase chain reaction amplification of indicated TTC7A exons from genomic DNA. (I) In vitro proliferation analysis of CD4⁺ and CD8⁺ T cells from patients after TCR stimulation. Proliferation history was monitored by flow cytometry–based detection of intracellular violet proliferation dye (VPD) dilution on day 3 (P1; left) and on day 4 (P2; right) after stimulation. Numbers above histograms indicate cell divisions. T-cell activation status was assessed by detection of CD25 on cell surface. HD, healthy donor.