RESUMO
Durante el desarrollo de un individuo se expresan distintas cadenas de globina de tipo a y no-a, que se combinan en tetrámeros para formar hemoglobina. Los genes que las codifican se organizan en familias. Distintas mutaciones afectan los genes que codifican las cadenas de globina: si provocan alteraciones cualitativas originan cuadros de hemoglobinopatías estructurales, si disminuyen las síntesis de las cadenas de globina, talasemias, y si tienen ambos efectos, hemoglobinopatías talasémicas. El propósito de este trabajo es presentar las bases moleculares de las hemoglobinopatías en Argentina, en un total de 862 muestras, en base a los estudios moleculares realizados en este laboratorio a partir del estudio de 910 muestras de pacientes. En nuestro medio, la Hb S es la hemoglobinopatía estructural más frecuente, las ß-talasemias presentan una distribución similar a la cuenca del Mediterráneo y las a-talasemias están intrínsecamente relacionadas a la ascendencia de los afectados. Las bases moleculares de las hemoglobinopatías son variadas. Mientras que en las hemoglobinopatías estructurales y ß-talasemias predominan las mutaciones puntuales, en las a-talasemias predominan las deleciones. Se describen mutaciones nóveles (cambios puntuales, deleciones y duplicaciones) que se presentan como eventos aislados con herencia recesiva o dominante. Es necesaria la interacción entre el médico hematólogo, el laboratorio bioquímico, el laboratorio molecular y el médico genetista, para llegar al diagnóstico certero de estos cuadros que permitirán reducir la incidencia de las formas severas.
Functional hemoglobin is a tetramer composed of 2 a and 2 non-a chains, encoded by genes that are organized in clusters and are expressed sequentially through development. There are multiple mutations described that affect these genes: if the sequence variant leads to a qualitative alteration, the resulting effect is a structural hemoglobinopathy, if it decreases the synthesis of the globin chains, thalassemia, and if it affects both the quality and quantity of the globin chain, the consequence is a thalassemic hemoglobinopathy. The aim of this paper is to present the molecular bases of hemoglobinopathies in Argentina, determined in 862 patients, based on the results of the molecular studies carried out in our laboratory from the analysis of 910 samples. Hb S is the most frequent structural hemoglobinopathy, ß-thalassemia mutations exhibit a pattern similar to the one displayed by Mediterranean basin populations, and a-thalassemia mutations are intrinsically related to the ancestry of those affected. These syndromes exhibit diverse molecular bases: structural hemoglobinopathies and ß-thalassemia are a consequence, mostly of point mutations, whereas in a-thalassemia deletions prevail. Novel mutations (point changes, deletions and duplications) that occurred as isolated events, with recessive or dominant inheritance, were described. Interaction between the hematologist, the geneticist and both the clinical and molecular biology laboratories is necessary to reach an accurate diagnosis of these syndromes and reduce the incidence of severe forms.
Durante o desenvolvimento de um indivíduo expressam-se diversas cadeias de globina de tipo a e não-a, que se combinam em tetrámeros para formar hemoglobina. Os genes que as codificam são organizados em famílias. Diferentes mutações afetam os genes que codificam as cadeias de globina: se provocarem alterações qualitativas originam quadros de hemoglobinopatias estruturais, se diminuírem as sínteses das cadeias de globina, talassemias, e se tiverem ambos os efeitos, hemoglobinopatias talassêmicas. O propósito deste trabalho é apresentar as bases moleculares das hemoglobinopatias na Argentina, num total de 862 amostras, com base nos estudos moleculares realizados neste laboratório a partir do estudo de 910 amostras de pacientes. No nosso meio, a Hb S é a hemoglobinopatia estrutural mais frequente, as ß-talassemias apresentam uma distribuição similar à bacia do Mediterrâneo e as a-talassemias estão intrinsecamente relacionadas com a ascendência dos afetados. As bases moleculares das hemoglobinopatias são variadas. Enquanto nas hemoglobinopatias estruturais e ß-talassemias predominam as mutações pontuais, nas a-talassemias predominam as deleções. Descrevem-se mutações incipientes (mudanças pontuais, deleções e duplicações) que se apresentam como eventos isolados com herança recessiva ou dominante. É necessária a interação entre o médico hematólogo, o laboratório bioquímico, o laboratório molecular e o médico geneticista, para chegar ao diagnóstico certo desses quadros que permitirão reduzir a incidência das formas severas.
Assuntos
Humanos , Hemoglobinas/análise , Hemoglobinopatias , Hemoglobinopatias/diagnóstico , Argentina , Talassemia , HemoglobinasRESUMO
Objective To study the Doppler ultrasound measurement of fetal middle cerebral artery peak ve -locity in the prediction of fetal thalassemia clinical value .Methods 90 cases of singleton pregnancies who were diag-nosesed for light or thalassemia intermedia patients ,also including her spouse were selected as the observation group , while in the same period in our hospital ,pregnant women of singleton pregnancy detected by Doppler ultrasound who had had no thalassemia gene ,also including her spouse were selected as control group .Gestation fetal brain hemody-namics related indicators of (22.0 ±3.0)weeks were analyzed for both groups .Results The thalassemia fetal middle cerebral artery peak velocity averaged (52.06 ±11.03)cm/s,compared with the control group ,the difference was sig-nificant(χ2 =348.20,P0.05);Light with thalassemia intermedia fetal middle cerebral artery peak ve-locity had no significant difference compared with control group (χ2 =1.63, 5.79, P >0.05 ).Conclusion Doppler ultrasound used to detect fetal middle cerebral artery peak systolic velocity prediction thalassemia has the ad -vantages of valid,reliable,non-invasive,repeatable,which has broad application prospects .