RESUMEN
Cowden disease (CD) (MIM 158350), or multiple hamartoma syndrome, is a rare autosomal dominant familial cancer syndrome with a high risk of breast cancer. Its clinical features include a wide array of abnormalities but the main characteristics are hamartomas of the skin, breast, thyroid, oral mucosa and intestinal epithelium. The pathognomonic hamartomatous features of CD include multiple smooth facial papules, acral keratosis and multiple oral papillomas. The pathological hallmark of the facial papules are multiple trichilemmomas. Expression of the disease is variable and penetrance of the dermatological lesions is assumed to be virtually complete by the age of twenty. Central nervous system manifestations of CD were emphasized only recently and include megalencephaly, epilepsy and dysplastic gangliocytomas of the cerebellum (Lhermitte-Duclos disease, LDD). Early diagnosis is important since female patients with CD are at risk of developing breast cancer. Other lesions include benign and malignant disease of the thyroid, intestinal polyps and genitourinary abnormalities. To localize the gene for CD, an autosomal genome scan was performed. A total of 12 families were examined, resulting in a maximum lod score of 8.92 at theta = 0.02 with the marker D10S573 located on chromosome 10q22-23.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 10 , Síndrome de Hamartoma Múltiple/genética , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Mapeo Cromosómico , Femenino , Ligamiento Genético , Marcadores Genéticos , Síndrome de Hamartoma Múltiple/diagnóstico , Humanos , Escala de Lod , Masculino , Linaje , Polimorfismo Genético , Factores de Riesgo , Programas InformáticosRESUMEN
Quantitative analysis of a ligand-protein interaction relates binding to the free concentration of ligand molecules in solution. A theoretical analysis is presented herein, by which intermolecular interactions can be described as a function of the added concentrations of ligand molecules. Following this analysis, ligand binding displacement and saturation curves can be converted directly into a linear form, even when nonradioactively labeled ligands are used to detect the ligand-protein interaction. From the linearities obtained, relevant binding parameters, including the binding dissociation constant, can be calculated. On the basis of this analysis, binding parameters have been characterized for the interaction between biotin-protein A and immunoglobulins, using ELISA-type detection, and for the interaction of a fluorescently labeled fatty acid with a specific fatty acid binding protein.
