Biomedical subjects

J Burn

Publications and source records attributed to J Burn.

219 records · Page 13Linked to original sources

PubMedDate not supplied

Preferential deletion of exons in Duchenne and Becker muscular dystrophies.

Duchenne and Becker muscular dystrophy (DMD and BMD) genes are located in Xp21 on the short arm of the X chromosome. DMD patients display a much more severe clinical course than BMD patients, and yet about 10% of cases of each have been reported to have deletions for parts of the gene. Using a complementary DNA subclone of the DMD gene we have screened 66 DMD and BMD patients who had not previously shown deletions with the probes then available. Fifteen patients have a deletion of this part of the gene, indicating a higher deletion frequency in this region (22%). Exons were deleted in five severely affected DMD patients and in ten BMD patients. Significantly, most of these deletions begin in the same region of the cDNA, which implies that there is a common mechanism for the generation of many of these mutations. An apparently identical deletion in one family gave classical BMD in two brothers (presenting in their teens) and only very mild muscle weakness in their 86-year-old great-great-uncle. Taking these data together with data using the probes previously published, we are able to detect deletions directly in 40% of our families requiring antenatal diagnosis or carrier detection.

Adolescent↗

PubMedDate not supplied

The clinical [corrected] background of familial adenomatous polyposis. History, epidemiology, diagnosis and treatment.

Familial adenomatous polyposis (FAP) is a dominantly inherited genetic disorder predisposing to colon cancer through the early development of multiple adenomatous polyps in the large bowel. FAP is not restricted to the colon and rectum, but is a more complex disease which can potentially affect almost any organ not only with benign tumours but also with life threatening carcinomas. Desmoid tumours and gastroduodenal polyps and cancer are the two more worrying extracolonic manifestations of FAP. Recent advances in FAP knowledge, such as the report of congenital hypertrophy of the retinal pigment epithelium (CHRPE) or the APC gene identification, are very useful for screening and long-term follow-up of the patients through regional or national registries. Nutritional and pharmacological intervention trials are under way to assess potential new medical treatments of FAP. Surgery is still the only effective treatment for colorectal cancer prevention in FAP. The choice of a surgical procedure is controversial, but the introduction of total proctocolectomy with ileal pouch-anal anastomosis can be considered as a major advance in surgical treatment of FAP during the last decade.

Abnormalities, Multiple↗

PubMedDate not supplied

The genetic background of familial adenomatous polyposis. Linkage analysis, the APC gene identification and mutation screening.

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.

Adenomatous Polyposis Coli↗