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Inicio Gaceta Médica de Bilbao Diagnostico molecular del gen HFE de la hemocromatosis hereditaria
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Vol. 105. Núm. 3.
Páginas 85-93 (Enero 2008)
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Vol. 105. Núm. 3.
Páginas 85-93 (Enero 2008)
Acceso a texto completo
Diagnostico molecular del gen HFE de la hemocromatosis hereditaria
Molecular diagnosis of the haereditary hemochromatosis gen (HFE)
Herentziazko hemokromatosiaren HFE genearen diagnostiko molekularra
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A. San-Miguel
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asanmiguel@hispavista.com

Correspondencia: Dr. A. San Miguel-Hernández. Laboratorio de Análisis Clínicos. Hospital Universitario Rio Hortega., Avda Cardenal Torquemada s/n. 47010. Valladolid. Espa˜a UE.
, N. Alonso, B. Calvo, R. Iglesias, R. San-Miguel, F.J. Martín-Gil
Servicio de Análisis Clínicos. Hospital Universitario Rio Hortega. Valladolid. Espa˜a UE.
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Resumen

La hemocromatosis hereditaria (HH) es una enfermedad metabólica resultante de una acumulación excesiva de hierro en la sangre, el hígado, corazón y otros órganos. Está causada por mutaciones en el gen HFE. Las personas con HH llevan casi siempre dos copias de la mutación Cys282Tyr del gen HFE, o una copia de esa mutación y otra de la mutación His63Asp del mismo gen. Las personas con dos copias de la mutación His63Asp y las personas portadoras de una sola copia de cualquiera de las dos mutaciones no tienen un riesgo mayor de sufrir hemocromatosis que la poblacion normal. Una de cada 9 personas es portadora de alguna de estas mutaciones: lleva una copia del gen normal y otra con la mutación. Las personas con la enfermedad han recibido una copia mutante de cada uno de sus dos progenitores que, frecuentemente, son individuos portadores de la mutación que no presentan hemocromatosis.

A pesar de la alta incidencia de esta enfermedad (0,3%), la mayoría de los casos permanecen sin diagnosticar. Afortunadamente, la HH está entre las pocas enfermedades que tienen un tratamiento simple y efectivo si se diagnostica tempranamente. Bajo tratamiento, la esperanza de vida del paciente es normal.

La prueba de ADN permite la detección inequívoca tanto de personas portadoras de una copia de la mutación, con riesgo de tener hijos con la enfermedad, como de personas con dos copias de la mutación que ya presenta la enfermedad o que la desarrollarán con una altísima probabilidad en el futuro.

Los objetivos del diagnostico de HH consisten en el estudio molecular de las mutaciones del gen HFE y en el consejo genético. Se debe realizar consejo genético para informar al paciente y a la familia de la forma de herencia, las implicaciones de la enfermedad, riesgo genético. Se debe realizar la historia familiar, árbol genealógico y los test genéticos para clarificar el estado de los miembros de la familia.

Palabras clave:
Hemocromatosis hereditaria
análisis de mutaciones
Summary

Hereditary hemochromatosis (HH), also known as iron overload disease, is an inherited disorder in which iron accumulates in blood (because too much is absorbed by the intestines), liver, heart, pancreas, pituitary gland, joints and other tissues. HH is most often caused by a faulty gene on chromosome 6 named HFE. Most of affected individuals have two copies of the Cys282Tyr mutation of the HFE gene while only a low percentage of individuals have either one or two copies of the second mutation, which is called His6Asp.The individuals having two copies of His63Asp mutation and those having a only copy of any of both mutations have not more risk for hemochromatosis than that the normal people. One of each 9 people is carrier of some of these mutations: they have a copy of the normal gene and another one of the mutation. The people with the disease have received a mutant copy of each one of their two parents who, frequently, are individual carriers of the mutation which they do not display hemochromatosis. In spite of the high incidence of this disease (0.3%), most of the cases remain without diagnose. Luckily, HH is between the few diseases that with an earlier diagnosis have a simple and effective treatment. Under treatment, the life expectancy of the patient is normal.

The HH DNA test for screening of the general population lead to an unequivocal detection of either the carrying people having a copy of the mutation (with risk of having children with the disease) or the people with two copies of the mutation (those that displays the disease or that will with a highest probability develop it in the future).

Primary objectives in HH diagnosis are: to examine HFE mutations and to increase individual information on genetic risk. Genetic advice should be carried out to the patient and their family on the inheritance form, the implications of the disease and the genetic risk. Genealogical familiar history, genetic tree and genetic test should be realised to clarify the family situation.

Key words:
Hereditary hemochromatosis
mutations analysis
Laburpena

Herentziazko hemokromatosia (HH) odolean, gibelean, bihotzean eta beste organo batzuetan burdin gehiegi metatzetik sortzen den gaixotasun metabolikoa da. HFE genearen mutazioek eragiten dute. HH duten pertsonek HFE genearen Cys282Tyr mutazioaren bi kopia daramatzate ia beti, baita gene beraren His63Asp mutazioren beste bat ere. His63Asp mutazioaren bi kopia dituzten pertsonak eta bi mutazioen zeinahiren kopia bakarra duten pertsona eramaileek ez dute biztanleria normalak baino arrisku handiagoa hemokromatosia sufritzeko. 9 lagun bakoitzetik bat mutazio horietakoren baten eramailea da: gene normalaren kopia bat dute eta beste bat, mutazioduna. Gaixotasuna duten pertsonek guraso bakoitzetik kopia mutante bat jaso dute eta, sarritan, hemokromatosia ez duten mutazioaren eramaileak dira.

Gaixotasun honen intzidentzia handia izan arren (% 0,3), kasu gehienak ez dira diagnostikatzen.

Zorionez, HH goiz diagnostikatuz gero, tratamendu bakun eta eraginkorra duen gaixotasun gutxienetakoen artean dago. Tratamendu pean, gaixoaren bizi-itxaropena normala da.

ADN probak mutazioaren kopia baten eramaileak diren eta gaixotasuna garatuko duten seme-alabak izateko arriskua duten pertsonak huts egin gabe antzematen laguntzen du, baita jadanik gaixotasuna duten mutazioaren bi kopiak dituzten pertsonak edo etorkizunean probabilitate oso handiarekin garatuko dutenak ere. HH diagnostikoaren helburuak HFE genearen mutazioen azterlan molekularrean eta aholku genetikoan oinarritzen dira. Aholku genetikoa egin behar da gaixoari eta familiari herentzia motaren, gaixotasunaren inplikazioen eta arrisku genetikoaren berri emateko. Familiaren historia, zuhaitz genealogikoa eta test genetikoak egin behar dira familiako kideen egoera argitzeko.

Gako-hitzak:
Herentziazko hemokromatosia
mutazioen analisia
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