RESUMEN
Hemoglobinopathies and thalassemias are the most commonly encountered monogenic disorders of blood in humans, posing a major genetic and public health problem round the globe. Hb S (HBB: c.20A>T)-ß-thalassemia (ß-thal) is a compound aberrant heterozygosity with inconsistent phenotypic expression, which are poorly described and clinically mapped. Comprehensive genetic characterization of such a population is highly warranted for complete understanding of the clinical heterogeneity, disease prognosis and therapeutic management. In this study, Hb S-ß-thal (n = 60) patients, strictly defined by varying degrees of clinical presentations, were selected to evaluate their genotype-phenotype agreement. Furthermore, ß-globin (n = 120) and α-globin gene clusters (n = 60) were genetically characterized and statistically correlated with clinical terminologies to explain the clinical heterogeneity. Our results revealed the association of the Arab-Indian haplotypes with nine different frameworks of ß-thal together with the modulating role of α-thalassemia (α-thal). The study subjects, including carriers of ß-thal haplotype III [- - - - - - -] (8.0%), presented with varying severe patterns of clinical symptoms such as painful crisis, multiple infections and splenomegaly, as an outcome of significantly less Hb F and higher Hb S levels (p < 0.5). The study findings indicated that together with α-thal, ß-thal haplotypes and Hb F levels, may possibly provide a close justification to support the clinical heterogeneity in the study population.
Asunto(s)
Haplotipos , Hemoglobina Falciforme/genética , Talasemia alfa , Talasemia beta/genética , Árabes , Hemoglobinopatías/etnología , Hemoglobinopatías/genética , Heterocigoto , Humanos , Fenotipo , Población Blanca , Talasemia beta/etnologíaAsunto(s)
Enfermedad de la Hemoglobina SC/fisiopatología , Adulto , Femenino , Hemoglobina Fetal/genética , Hemoglobina A2/genética , Hemoglobina C/genética , Enfermedad de la Hemoglobina SC/sangre , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/genética , Enfermedad de la Hemoglobina SC/patología , Hemoglobina Falciforme/genética , Hepatomegalia/etiología , Hepatomegalia/genética , Hepatomegalia/fisiopatología , Humanos , Húmero/patología , India , Masculino , Osteonecrosis/etiología , Osteonecrosis/patología , Hermanos , Esplenomegalia/etiología , Esplenomegalia/genética , Esplenomegalia/fisiopatologíaRESUMEN
Hb D-Punjab [ß121(GH4)GluâGln] is prevalent in the northern states of the Indian subcontinent. Due to inadequate data from Asian countries, the origin and spread of the Hb D-Punjab mutation are uncertain. In a study of sickle cell hemoglobinopathies, we detected the Hb D-Punjab mutation in 25 subjects from 11 unrelated Agharia families. Twelve cases were Hb S [ß6(A3)GluâVal]/Hb D-Punjab compound heterozygotes and 13 were Hb D trait carriers. In 76.0% of the cases, the ß(D) gene was linked to haplotype I, whereas 24.0% had a novel haplotype. None of the haplotypes matched the ß(A) haplotype of the local population. In view of the ancestral origin of the subjects and the high prevalence of the ß(D) gene in the states of northern India, we suggest a North Indian origin for the ß(D) mutation in our population. The finding of a novel haplotype in eastern India supports the hypothesis of a multicentric origin of this mutation.
