RESUMEN
The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3' end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype-phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.
Asunto(s)
Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Diarrea Infantil/genética , Molécula de Adhesión Celular Epitelial/química , Síndromes de Malabsorción/genética , Modelos Moleculares , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Diarrea Infantil/patología , Molécula de Adhesión Celular Epitelial/genética , Células Epiteliales/metabolismo , Estudios de Asociación Genética , Humanos , Síndromes de Malabsorción/patología , Proteína 2 Homóloga a MutS/genética , Mutación Missense/genética , Sitios de Empalme de ARN/genéticaAsunto(s)
Esofagitis/etiología , Fiebre Mediterránea Familiar/diagnóstico , Úlcera Gástrica/etiología , Colchicina/uso terapéutico , Proteínas del Citoesqueleto/genética , Endoscopía Gastrointestinal , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/tratamiento farmacológico , Mucosa Gástrica , Humanos , Lactante , Masculino , Pirina , Moduladores de Tubulina/uso terapéuticoRESUMEN
OBJECTIVES: The clinical importance and etiology of colonic lymphoid nodular hyperplasia (LNH) are not clear. It has been considered a response to some antigenic stimuli. Although food allergies, infections, inflammatory bowel diseases, and immunodeficiencies may be listed in the etiology of colonic LNH, the etiology has remained unclear in many cases. This study investigated the etiology of colonic LNH and its relation to familial Mediterranean fever (FMF) in children. FMF as an etiologic factor for colonic LNH has not been reported before in the literature. METHODS: Medical files of patients who underwent colonoscopy between 2007 and 2011 were examined retrospectively. Demographic features, presenting symptoms, colonoscopy indications, colonoscopic findings, and final diagnoses of patients were evaluated. According to etiologies, patients with colonic LNH were divided into 2 groups: group A consisted of patients with FMF and group B consisted of diseases other than FMF. RESULTS: A total of 311 patients were included in the study. Forty (12.6%) patients had isolated colonic LNH. In 23 (57.5%) patients, isolated LNH was observed in some colonic segments and total colonic LNH was noted in 17 (42.5%) patients. FMF was the etiologic factor in 6 (15%) patients. Thirty-four patients (85%) had etiologic factors other than FMF. We did not find any etiologic factor for LNH in 3.53% (11/311) of patients. CONCLUSIONS: FMF may be an etiologic factor for colonic LNH in children besides food allergies, infections, inflammatory bowel diseases, and immunodeficiencies.