RESUMEN
Familial hypobetalipoproteinemia is an autosomal codominant trait that can be caused by mutations in the apo B gene. Here we report a novel apo B gene mutation causing hypobetalipoproteinemia, that is associated with the synthesis of a truncated apo B protein in a young healthy male subject and his mother. The mutation is an A deletion at position 6627 of the apo B cDNA leading to a truncated protein of 2166 amino acids (apo B-48.4). This truncated apo B was detected mainly in VLDL, LDL and in trace amounts in HDL, but not in the lipoprotein deficient plasma fraction. Affected family members present with elevated levels of HDL-cholesterol, mainly due to an increase in HDL2 particles. Postprandial triglycerides and retinyl esters in the d < 1.006 g/ml lipoprotein in the proband showed a normal response to an oral fat load compared to a group of eight matched healthy controls. In summary this novel mutation is associated with hypobetalipoproteinemia with a normal fat absorption as expected for a protein with a length similar to that of apo B-48.
Asunto(s)
Apolipoproteínas B/genética , Hipobetalipoproteinemias/genética , Oligopéptidos/genética , Adulto , Anciano , Apolipoproteína A-I/sangre , Apolipoproteína A-II/sangre , Apolipoproteína B-48 , Apolipoproteína C-II , Apolipoproteína C-III , Apolipoproteínas B/análisis , Apolipoproteínas B/sangre , Apolipoproteínas B/química , Apolipoproteínas C/sangre , Apolipoproteínas E/sangre , Apolipoproteínas E/genética , Secuencia de Bases , Colesterol/sangre , HDL-Colesterol/sangre , HDL-Colesterol/genética , LDL-Colesterol/sangre , LDL-Colesterol/genética , VLDL-Colesterol/sangre , VLDL-Colesterol/genética , Análisis Mutacional de ADN , ADN Complementario/análisis , ADN Complementario/genética , Electroforesis en Gel de Poliacrilamida , Salud de la Familia , Femenino , Eliminación de Gen , Humanos , Inmunoquímica , Masculino , Persona de Mediana Edad , Madres , Oligopéptidos/química , Linaje , Fenotipo , Mutación Puntual/genética , Mutación Puntual/fisiología , Dodecil Sulfato de Sodio , Triglicéridos/sangreRESUMEN
Hyperprolactinaemia is the most common result of pituitary dysfunction and is characterized by alteration on the reproductive function. After a review of the hypothalamic control mechanisms and of the local paracrine and autocrine factors regulating prolactin secretion, the most common physiological, pharmacological and pathological causes of hyperprolactinaemia are described. The clinical pictures of hyperprolactinaemia in man and woman are then summarized. The diagnostic protocol used in this Institute is then described: confirmation of the existence and entity of hyperprolactinaemia by means of a prolactin profile; exclusion of pharmacological or extra pituitary causes (cirrhosis, primitive hypothyroidism, chronic renal failure, etc.); neuro-radiological evaluation of the sella region, by means of standard X-ray, computer tomography scan, nuclear magnetic resonance. The drugs commonly used in medical treatment of hyperprolactinaemia such as a bromocriptine, other-derived compounds and then recent CV 205-502, and the surgical approaches (trans-sphenoidal and transcranial routes) are reported. The indication of medical or surgical treatment and the relevance of radiotherapy are finally considered.