ABSTRACT
A human aniridia candidate (AN) gene on chromosome 11p13 has been cloned and characterized. The AN gene is the second cloned gene of the contiguous genes syndrome WAGR (Wilms' tumor, aniridia, genitourinary malformations, mental retardation) on chromosome 11p13, WT1 being the first gene cloned. Knowledge about the position of the AN and WT1 genes on the map of 11p13 makes the risk assessment for Wilms' tumor development in AN patients possible. In this study, we analyzed familial and sporadic aniridia patients for deletions in 11p13 by cytogenetic analyses, in situ hybridization, and pulsed field gel electrophoresis (PFGE). Cytogenetically visible deletions were found in 3/11 sporadic AN cases and in one AN/WT patient, and submicroscopic deletions were identified in two sporadic AN/WT patients and in 1/9 AN families. The exact extent of the deletions was determined with PFGE and, as a result, we could delineate the risk for Wilms' tumor development. Future analyses of specific deletion endpoints in individual AN cases with the 11p13 deletion should result in a more precise risk assessment for these patients.
Subject(s)
Aniridia/genetics , Chromosome Deletion , Genes, Wilms Tumor/genetics , Kidney Neoplasms/genetics , Wilms Tumor/genetics , Adolescent , Child , Chromosome Mapping , DNA Probes , Female , Humans , In Situ Hybridization , Infant , Karyotyping , MaleABSTRACT
A 46 year old AIDS-patient, who had developed CMV-retinitis was treated with the virostatic drug dihydroxypropoxymethylguanine (DHPG, Ganciclovir) over a period of 16 months until he died due to a pneumonia. After the DHPG-treatment was initiated the retinitis improved markedly, however there still was a very slow progression of the disease in the following time. The central retina of both eyes was not affected until death. Postmortal immunohistochemically CMV-antigen-staining was positive according to the former clinically active retinitis. At the eyes of the retinal necrosis calcified deposits were identified by Kossa-staining; these areas had clinically appeared as yellowish briddle deposits. The clinical course and the immunohistochemical proof of active CMV-virus-particles suggest that DHPG was able to suppress the progression of a CMV-retinitis and to preserve a good visual acuity until death; however a true cure of the CMV-infection could not be achieved.
Subject(s)
Cytomegalovirus Infections/pathology , Cytomegalovirus/drug effects , Ganciclovir/therapeutic use , HIV Infections/pathology , Opportunistic Infections/pathology , Retinitis/pathology , Antibodies, Viral/analysis , Cytomegalovirus/immunology , Cytomegalovirus Infections/drug therapy , Fluorescein Angiography , Humans , Immunoenzyme Techniques , Male , Middle Aged , Opportunistic Infections/drug therapy , Retina/pathology , Retinitis/drug therapy , Visual Acuity/drug effects , Visual Fields/drug effectsABSTRACT
The clinical course of 3 patients treated with the virostatic drug dihydroxypropoxymethylguanine (DHPG) is reported. With maintenance therapy the progression of retinitis was slow, but was not stopped. More rapid progression of retinitis could be observed after cessation of therapy because of DHPG-induced leukopenia. Therefore, consequent maintenance therapy should be the therapeutic aim. Under maintenance therapy, useful visual acuity could be maintained until death.
