RESUMEN
AIM: To study the relationship between the genotype and the phenotype in the patients with Hermansky - Pudlak syndrome (HPS) associated with granulomatous colitis; to monitor clinical course of the disease for adequate treatment, cancer surveillance and genetic counseling. MATERIALS AND METHODS: The diagnosis of HPS is established by physical examination, chest X-ray, computed tomography, endoscopic examination with biopsy, and laboratory tests, including histology, baseline laboratory blood, urine and feces tests, determination of ASCA-C and ANCA antibodies using an ELISA. Molecular genetic testing for HPS gene mutations, R702W, G908R, L1007fs and P268S mutations in NOD2 gene, and TaqI variant of the VDR gene were carried out. RESULTS: We report 2 cases of HPS from unrelated families. Both were complicated by inflammatory bowel disease with pathologic features of Crohn's disease refractory to antibiotics and corticosteroids. One patient (family 1) with Ashkenazi Jewish ancestry had pathogenic variant of the HPS-4 gene in exon 8, mutation P268S of NOD2 genes and "Tt" genotype of TaqI variant of the VDR gene. Another patient (family 2) carried two mutations P268S and G908R of NOD2 gene, and had a large paraovarian cyst diagnosed. No consistent success with the standard medical therapy, used for treating granulomatous colitis, associated with HPS, in presented cases was achieved. Patients needed surgical interventions at a young age and a long-term surveillance of the probable development of tumors and other complications. Azathioprine at 2 mg/kg/day and mesalazine 3 g/day were used with some positive effect for prevention of Crohn's disease postoperative recurrence. CONCLUSION: The occurrence of perianal lesions, the histopathological findings and the results of the molecular genetic analysis confirmed the mutations P268S and G908R of NOD2 gene in these cases suggest that HPS was truly associated with Crohn's disease variant with early onset and severe course. The search for the molecular causes of the disease in some individuals may help in the development of new therapeutic and surgical approaches, as well in the improvement of understanding of premalignant inflammatory conditions in a large bowel.
Asunto(s)
Colitis/genética , Síndrome de Hermanski-Pudlak/patología , Proteína Adaptadora de Señalización NOD2/genética , Adolescente , Adulto , Colitis/patología , Femenino , Genotipo , Síndrome de Hermanski-Pudlak/genética , Humanos , Mutación , Linaje , FenotipoRESUMEN
UNLABELLED: The aim of the study was to improve cytogenetic diagnostics and monitoring of myelofibrosis and to reveal the spectrum of cytogenetic abnormalities in patients from Ukraine. MATERIALS AND METHODS: A total of 42 patients (23 females and 19 males) with myelofibrosis was studied using different cytogenetic methods. Granulocyte colony-stimulating factor (G-CSF) was added by the new method during cultivation of peripheral blood (PB) cells from 31 patients for specific stimulation of mitotic divisions. Two patients underwent examination by fluorescent in situ hybridization method. RESULTS: In cell cultures of PB stimulated in vitro with G-CSF and in non-stimulated bone marrow chromosome abnormalities were found in 19 (45.2%) of all the patients. The spectrum of cytogenetic abnormalities of bone marrow and PB was the same in all of the patients. Aspiration of bone marrow was unsuccessful due to significant fibrosis in 10 (29.4%) of 34 patients. The study by fluorescent in situ hybridization method confirmed cytogenetic abnormalities revealed by G-method and discovered additional possibly normal subclone. CONCLUSIONS: Cytogenetic study of PB using in vitro G-CSF as a specific stimulant of mitosis instead of phytohemagglutinin revealed significant variety of chromosomal abnormalities in Ukrainian patients with myelofibrosis. This method could be a less invasive alternative to cytogenetic examination of bone marrow in the subgroup of patients with considerable fibrosis and consecutive changes. The usage of fluorescent in situ hybridization method supplemented karyotyping by G-banding method.
Asunto(s)
Células Sanguíneas/patología , Médula Ósea/patología , Aberraciones Cromosómicas , Análisis Citogenético/métodos , Factor Estimulante de Colonias de Granulocitos/metabolismo , Mielofibrosis Primaria/genética , Células Sanguíneas/metabolismo , Médula Ósea/metabolismo , Células Cultivadas , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/metabolismo , Mielofibrosis Primaria/patologíaRESUMEN
AIM: To describe the case of metachronous gastrointestinal stromal tumors in a proband with familial adenomatous polyposis (FAP), carrier of APC gene mutation in codon 1309. MATERIAL AND METHODS: The physical examination, genealogical analysis and molecular genetic analysis of peripheral blood in 15-years-old girl with FAP and her sister, were carried out. Macroscopic, standard histological and immunohistochemical study of surgical specimens - intraintestinal tumors of the small intestine in proband was performed. RESULTS: Extraintestinal manifestations, including congenital abnormalities of facial skeleton, typical for Gardner's syndrome, were observed in the sisters with FAP as the addition symptoms of the disease. Frameshift mutation in codon 1309 in the APC gene was detected in these patients. A rare neoplasia - metachronous gastrointestinal stromal tumor was found in proband 15 months after total colectomy for FAP. This is the third case described in the accessible medical literature. CONCLUSION: The possible role of APC gene mutation in the development of mesenchymal neoplasms is discussed. The study of stromal tumors is important for understanding of their pathogenesis that will enable to develop effective targeted therapy.