Asunto(s)
Duplicación de Gen , Patrón de Herencia , Familia de Multigenes , Globinas alfa/genética , Talasemia beta/genética , Alelos , Estudios de Asociación Genética , Genómica/métodos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Linaje , Talasemia beta/diagnósticoRESUMEN
To help clarify the hematological picture of patients who may be positive for beta- and delta-globin gene mutations, the following study was carried out. Our aim was to identify the delta-globin gene mutations found in the Greek Cypriot population, their frequencies and the Hb A2 values associated with them. Seventy-four samples were selected from a random sample of 5,030 individuals, and the database of the Molecular Genetics Thalassaemia Department containing diagnostic analyses data was also mined for relevant information. Four novel for Cyprus delta-globin gene mutations: -30 (T-->C), Hb A2-Wrens [delta98(FG5)Val-->Met, GTG-->ATG], IVS-I-2 (T-->C) and Hb A2-Yokoshima [delta25(B7)Gly-->Asp (GGT-->GAT)] were identified. Hb A2-Yialousa [delta27(B9)Ala-->Ser, GCC-->TCC], Hb A2-Yokoshima, Hb A2-Troodos [delta116(G18)Arg-->Cys, CGC-->TGC], Hb A2-Pelendri [delta141(H19)Leu-->Pro, CTG-->CCG], codon 4 [delta4(A1)Thr-->Ile], codon 59 (-A), Hb A2-Wrens, IVS-II-897 (A-->G), IVS-I-2, -55 (T-->C) and -30 bring the total to 11 delta-globin alleles found in the Greek Cypriot population. Hb A2-Yialousa is the most common mutation followed by codon 4, with frequencies of 60.7 and 17.8%, respectively.Hb A2 levels above 1.9% have been found to indicate a significantly reduced possibility for the presence of a delta-globin gene mutation in this population. For Hb A2 levels of 1.7 and 1.8% the possibility of a delta-globin gene mutation rises to 90.9% and reaches 100% for lower Hb A2 levels. The frequency of all the mutant delta-globin chromosomes in the sample is 0.0067 and the carrier frequency is 1.26%.