THE ASSOCIATION OF ALPHA-THALASSEMIA AND BETA-THALASSEMIA WITH A GENETRIPLICATION IN ONE FAMILY

BACKGROUND: We describe the haematological data and molecular results of a native familiy from Cadiz in that one is produced the a within he terozygous beta degrees thalassaemia (IVS-1, nt 1-G-->A), heterozygous alpha(+) thalassaemia (-alpha(3.7)) and alpha gene triplication (alph a alpha alpha(3.7)). PATIENTS AND METHODS: We are studied 7 members to a family composed by father (I-1), mother (I-2) and five children (II 1, II2, II3, II4, II5). The molecular biology study of the alpha gene was realyzed by Southern blot method using the restriction enzymes Ram HI, Bgl II and Eco RI and hybridazed with or probe of the plasmide PR B 1 (fragment of 1,5 Kb digested with the enzyme Pst I), The genes wer e studied by the technique of the polymerase chain reaction (PCR), mod ified according to designated method ''Amplification Refractory Mutati on System'' (ARMS). RESULTS: The father (I-1) presents an interaction of therozygous beta degrees thalassaemia with heterozygous alpha(+) th alassaemia (beta degrees/beta 1;alpha alpha/-alpha(3.7)). The mother ( I-2) shows an alpha gene triplication (beta(A)/beta(A);alpha alpha alp ha(3.7)/alpha alpha). Finally the children are expressed 5 possibiliti es: II4 he is normal (beta(A)/beta(A);alpha alpha/alpha alpha), II2 he has alpha gene triplication (beta(A)/beta(A);alpha alpha/alpha alpha alpha(3.7)) II3 he has heterozygous beta degrees thalassaemia (beta de grees/beta(A);alpha alpha/alpha alpha), II5 he has interaction between heterozygous beta degrees thalassaemia and heterozygous alpha gene tr iplication (beta degrees/beta(A);alpha alpha alpha(3.7)/alpha alpha), and II1 presents an interaction between a heterozygous beta degrees th alassaemia and together with the lost of one a gene in one chromosome he also presents a alpha gene triplication in other one (beta degrees/ beta(A);alpha alpha/alpha alpha). The haematologycal data of II5 corre sponds to a intermediate thalassemia with not transfusion dependent fe ature an opposite to II1 that presents a heterozygous thalassemic trai t features with 4 alpha genes. DISCUSSION: The fenotypical expression of the different interactions of these mutations in this family, point s out, the relevant role that the unbalance globins chains plays in th e pathogenesis and development of the clinical manifestations of the p atients with the thalassaemia syndromes.