RESUMEN
Familial adenomatous polyposis (FAP) is characterised by hundreds of colorectal adenomas. Endocrine neoplasms have occasionally been reported, as have gastric polyps, which are usually hamartomatous in the fundus of the stomach and adenomatous in the antrum. A 57 year old man with colorectal, gastric, and periampullary adenomatous polyposis, in association with three bilateral adrenocortical adenomas, is presented. Mutation screening showed a 5960delA germline mutation in the adenomatous polyposis coli (APC) gene predicted to lead to a premature stop codon. This mutation was found in three of the four children of the patient. Western blot analysis of a lymphoblastoid cell line derived from the patient failed to detect any truncated APC polypeptide. This rare 3' mutation is responsible for an unusually complex and late onset phenotype of FAP.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Adenoma Corticosuprarrenal/genética , Genes APC , Mutación de Línea Germinal , Poliposis Adenomatosa del Colon/patología , Adenoma Corticosuprarrenal/patología , Análisis Heterodúplex , Humanos , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Análisis de Secuencia de ADNRESUMEN
As previously reported, a C-type retrovirus, referred to as retrovirus X was isolated from HIV infected cells. In order to further characterize this virus, the proviral DNA was cloned and sequenced. The organization of the genome (8379 bp) appeared to be typical of the mammalian type C retroviruses. The virus was shown to be closely related to the gibbon ape leukaemia virus (GALV) with 87% similarity when the sequence was compared with the published genome of the Seato strain of GALV. At the level of the long terminal repeat where comparison was possible with other strains, the closest relationship was found with the San Francisco strain of GALV and with the simian sarcoma virus. These results suggest that the isolate should be considered as a strain of GALV.
Asunto(s)
ADN Viral/química , Gammaretrovirus/genética , Provirus/genética , Secuencia de Aminoácidos , Secuencia de Bases , Línea Celular , Clonación Molecular , VIH/crecimiento & desarrollo , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
Among 23 germline mutations identified in the APC screening of 45 familial adenomatous polyposis (FAP) patients, we have found 10 different novel frameshift mutations in 11 apparently unrelated patients. In two cases, an additional missense mutation was detected. One previously described as a causative germline mutation (S2621C), associated with a 1-bp insertion (4684insA) on the opposite allele, did not segregate with the FAP phenotype in the family and was therefore considered as being non-pathogenic. The other (Z1625H) was located 2 codons before a 1-bp deletion (4897delC). Both mutations were transmitted together from an FAP father to his affected son. The FAP phenotype of these 10 novel truncating mutations was clinically documented within their kindreds. Important variability was observed in the phenotype. Interestingly, we noted that a mutation (487insT) localized at the boundary of the 5' attenuated APC phenotype region in two unrelated families resulted in classical polyposis. A clear-cut genotype-phenotype correlation could be drawn in only two instances. In one family, a 4684insA mutation led to a mild polyposis associated with early inherited osteomas and, in the family bearing the double mutation (Z1625H + 4897delC), the phenotype was obviously a 3' attenuated type. Our data illustrate the wide genetic and phenotypic heterogeneity of this condition between and within the families, making the establishment of correlations complex and any prediction in this disease difficult, although targeting the mutation site may be helpful in some specific cases.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Genes APC/genética , Heterogeneidad Genética , Mutación de Línea Germinal/genética , Poliposis Adenomatosa del Colon/patología , Anciano , Femenino , Humanos , Masculino , FenotipoRESUMEN
The few studies concerning HCV genotypes in hemodialyzed patients concerned small groups of patients, issued from single units. Using the RFLP typing method in the 5' non-coding region (5' NCR), we performed the genotyping of HCV strains of 80 patients issued from 14 Belgian dialysis units. Forty-seven of the 80 patients were also tested by Inno-Lipa II (Innogenetics, Gent, Belgium). Sixty-four of 80 patients (80%) were infected with subtype 1b, 2 (2.5%) with subtype 1a, 6 (7.5%) with subtype 2a and 1 (1%) with subtype 2b; 6 patients (7.5%) showed a type 4 and 2 patients (2.5%) a type 5 infection, respectively. Only 1 patient (1%) showed a mixed infection (1a and 1b). In the 47 patients tested by both methods, we observed a very good agreement (98%) between RFLP and Inno-Lipa II's results. Our multicentric study detected HCV genotypes 4 or 5 in 8/80 (10%) of hemodialyzed patients in Belgium. The substantial prevalence of these genotypes could not be fully explained by a nosocomial spread of HCV infection: indeed, four patients belonged to dialysis units located in different cities, and two appeared infected with distinct subtypes in a same unit. Thus, the discovery of a "rare" HCV genotype in several hemodialyzed patients does not always point to nosocomial HCV transmission.
Asunto(s)
Hepacivirus/genética , Hepatitis C/virología , Diálisis Renal , Bélgica/epidemiología , Genotipo , Hepatitis C/epidemiología , Hepatitis C/transmisión , Humanos , Incidencia , Polimorfismo de Longitud del Fragmento de Restricción , PrevalenciaRESUMEN
Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disease that predisposes to colorectal cancer and is characterized by the presence of hundreds to thousands of adenomas covering the colon and rectum. Mapping of the FAP locus to 5q21-q22 by linkage studies in families ultimately allowed the identification of the APC (Adenomatous Polyposis Coli) gene itself. The APC gene comprises 15 exons with a 9 kilobase RNA transcript and a 312 kilodalton final protein product. This discovery transformed the diagnosis of FAP and offered direct identification of defective gene carriers by mutation screening. Currently used techniques have been successful in detecting mutations in 15 to 67 percent of patients. To date, at least 136 different mutations have been described in 301 unrelated FAP patients, most of which (98%) are translation terminating mutations leading to a truncated final protein product. Promising applications or development of novel procedures, like the protein truncation test (PTT), are under way for the remaining FAP patients. With the exception of the description of a critical boundary in exon 9 for the presence or absence of CHRPE, there are no clear genotype-phenotype relationships, but mutations located in the 5' half of exon 15 seem to lead to a more severe phenotype. Very little is know about the APC protein product function. The APC protein could be involved in cell-to-cell signalling and/or cell adhesion functions. The APC gene is a tumour suppressor gene involved in early stages of sporadic colorectal carcinogenesis. Further understanding of the APC gene function may define a rational approach for early detection, prevention strategies, assessment of prognosis and treatment of colorectal cancer. In this regard, animal models of FAP, like the MIN (Multiple Intestinal Neoplasia) mouse or the APC 1638 mouse, are promising and powerful tools.
Asunto(s)
Poliposis Adenomatosa del Colon/genética , Genes APC , Secuencia de Bases , Análisis Mutacional de ADN , Genes Dominantes , Tamización de Portadores Genéticos , Ligamiento Genético , Humanos , Datos de Secuencia Molecular , Mutación PuntualRESUMEN
Autosomal recessive polycystic kidney disease (RPKD) (also called infantile polycystic kidney disease) and autosomal dominant polycystic kidney disease (DPKD) (or adult form) are the two main types of genetic polycystic kidney diseases (PKD) encountered in children and infants. We report here a case of DPKD with no family history and discuss the main features leading to the differential diagnosis between these two types of PKD, their prognosis and the importance of making the right diagnosis for the genetic counselling.
Asunto(s)
Riñón Poliquístico Autosómico Dominante/diagnóstico , Alelos , Femenino , Humanos , Lactante , Pruebas de Función Renal , Riñón Poliquístico Autosómico Dominante/genética , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Spontaneous mutants of Escherichia coli K12 displaying an increased level of the kanamycin resistance conferred by plasmid pGR71 were selected. Several mutants obtained in this way apparently carry large chromosomal deletions extending into galU and/or bglY (27 min). This positive selection of deletions allowed detection of a new locus located between galU and bglY. Deletions of this locus are responsible for increased resistance to kanamycin (Irk), decreased resistance to L-serine in minimal medium (Drs) and decreased resistance to chloramphenicol (Drc) when a cat gene is present in the bacteria.