RESUMO
A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Mutação em Linhagem Germinativa , Sequenciamento de Nucleotídeos em Larga Escala , Adulto , Idoso , Neoplasias Colorretais/genética , DNA Polimerase II/genética , DNA Polimerase III/genética , Saúde da Família , Feminino , Deleção de Genes , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Linhagem , Proteínas de Ligação a Poli-ADP-Ribose/genética , Tunísia , Adulto JovemRESUMO
Collagenous gastritis is a rare entity, characterized by the deposition of a subepithelial collagenous band with an inflammatory infiltrate in the mucosa. We report the first Tunisian case revealed by severe anemia. Lesions were limited to the stomach and remained unchanged on 3 series biopsies during a 24 month follow up despite treatment with corticosteroids. The cause of the disease remains unknown; our findings suggest that lesions of collagenous gastritis may result from a local immune process.
Assuntos
Anemia/etiologia , Doenças do Colágeno/diagnóstico , Gastrite/diagnóstico , Biópsia , Colágeno/metabolismo , Doenças do Colágeno/tratamento farmacológico , Doenças do Colágeno/fisiopatologia , Seguimentos , Gastrite/tratamento farmacológico , Gastrite/fisiopatologia , Glucocorticoides/uso terapêutico , Humanos , Masculino , Tunísia , Adulto JovemRESUMO
We describe three cases of osteomalacia presenting in Tunisian women, all of whom had previously-undiagnosed coeliac disease (CD). Direct enquiry revealed an important weight loss and a history of diarrhoea in two patients, and a 15-year history of anaemia in one patient. Laboratory tests showed severe anaemia in the three cases. Reduced calcium was found in two cases, and corrected calcium was found in one case. Radiological examination showed fissure in two cases. The diagnosis of osteomalacia was made by clinical, biochemical and radiological features. Antigliadin, antireticulin, antiendomysial and anti-tissue transglutaminase antibodies were all positive in the three cases, and a small-bowel biopsy confirmed the diagnosis of CD. Treatment with gluten-free diet (GFD), supplemental calcium and vitamin D was initiated for the three patients, but only one patient complies strictly with the GFD; she showed a marked resolution of her symptoms.
