TY - JOUR
T1 - The gastrointestinal manifestations of telomere-mediated disease
AU - Jonassaint, Naudia L.
AU - Guo, Nini
AU - Califano, Joseph A.
AU - Montgomery, Elizabeth A
AU - Armanios, Mary
PY - 2013
Y1 - 2013
N2 - Defects in telomere maintenance genes cause pathological telomere shortening, and manifest in syndromes which have prominent phenotypes in tissues of high turnover: the skin and bone marrow. Because the gastrointestinal (GI) epithelium is highly proliferative, we sought to determine whether telomere syndromes cause GI disease, and to define its prevalence, spectrum, and natural history. We queried subjects in the Johns Hopkins Telomere Syndrome Registry for evidence of luminal GI disease. In sixteen percent of Registry subjects (6 of 38), there was a history of significant GI pathology, and 43 additional cases were identified in the literature. Esophageal stenosis, enteropathy, and enterocolitis were the recurrent findings. In the intestinal mucosa, there was striking villous atrophy, extensive apoptosis, and anaphase bridging pointing to regenerative defects in the epithelial compartment. GI disease was often the first and most severe manifestation of telomere disease in young children. These findings indicate that telomere dysfunction disrupts the epithelial integrity in the human GI tract manifesting in recognizable disease processes. A high index of suspicion should facilitate diagnosis and management.
AB - Defects in telomere maintenance genes cause pathological telomere shortening, and manifest in syndromes which have prominent phenotypes in tissues of high turnover: the skin and bone marrow. Because the gastrointestinal (GI) epithelium is highly proliferative, we sought to determine whether telomere syndromes cause GI disease, and to define its prevalence, spectrum, and natural history. We queried subjects in the Johns Hopkins Telomere Syndrome Registry for evidence of luminal GI disease. In sixteen percent of Registry subjects (6 of 38), there was a history of significant GI pathology, and 43 additional cases were identified in the literature. Esophageal stenosis, enteropathy, and enterocolitis were the recurrent findings. In the intestinal mucosa, there was striking villous atrophy, extensive apoptosis, and anaphase bridging pointing to regenerative defects in the epithelial compartment. GI disease was often the first and most severe manifestation of telomere disease in young children. These findings indicate that telomere dysfunction disrupts the epithelial integrity in the human GI tract manifesting in recognizable disease processes. A high index of suspicion should facilitate diagnosis and management.
KW - Dyskeratosis congenita
KW - Enterocolitis
KW - Hoyeraal-Hreidarsson syndrome
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=84878941304&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878941304&partnerID=8YFLogxK
U2 - 10.1111/acel.12041
DO - 10.1111/acel.12041
M3 - Article
C2 - 23279657
AN - SCOPUS:84878941304
SN - 1474-9718
VL - 12
SP - 319
EP - 323
JO - Aging Cell
JF - Aging Cell
IS - 2
ER -