Bases moleculares de las alteraciones genéticas que afectan la síntesis de hemoglobina
Over 700 samples from carriers of structural hemoglobinopathies and thalassemia, and affected individuals with these syndromes, were analyzed.\nThe frequency of ?-thalassemia was updated: mutations were detected in 417 families; 9 mutations were described for the first time in Argentina.\nFive mutat...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2015
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_1162 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1162.dir/1162.PDF |
| Aporte de: |
| Sumario: | Over 700 samples from carriers of structural hemoglobinopathies and thalassemia, and affected individuals with these syndromes, were analyzed.\nThe frequency of ?-thalassemia was updated: mutations were detected in 417 families; 9 mutations were described for the first time in Argentina.\nFive mutations associated with dominant forms of ?-thalassemia were detected: Hb Durham-N.C., and 4 novel mutations: Hbs Tavapy(HBB:c.182_187delCTCATG), JC-Paz(HBB:c.34_42delGTTACTGCC), Wilde (HBB:c.270_273delTGAG) and Patagonia(HBB:c.296_297dupGT).\nDeletions are the most common ?-thalassemic mutations (-?3,7, --MEDI, --CAL/CAMP and ?SEA). Three novel deletions were characterized: --BA, --PA and ?LU. The last one was identified in a boy with phenotypic features consistent with ATR-16. Point mutations were detected in both HBA genes; 3 novel mutations were detected: HBA1:c.301-2A>T, HBA1:c.187delG(p.W62fsX66) and HBA1:c.237delC(p.Asn78Lysfs*6).\nHb S is the most frequent structural hemoglobinopathy; mutations leading to unstable hemoglobins, hemoglobins with increased oxygen affinity and Hb M were detected, sporadically.\nGenotype-Phenotype association studies were performed to evaluate loci involved in Hb F levels variation.\nPrimary, secondary and tertiary genetic modifiers were analyzed in patients with thalassemia intermedia. Two novel ?-globin cluster duplications were detected.\nGenotype-Phenotype profiles were made and algorithms for molecular characterization were established.\nHopefully, this work will result in benefit of the affected families. |
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