RED-CELL DIMORPHISM IN A YOUNG MAN WITH A CONSTITUTIONAL CHROMOSOMAL TRANSLOCATION T(1122)(P15.5Q11.21)

A constitutional, balanced chromosomal translocation t(11;22)(p15.5;q1 1.21) was discovered in a tall young man during investigation of a red cell dimorphism. The red cells are predominantly normochromic and nor mocytic with a small population of hypochromic, microcytic cells. Cont ained within the regions involved in the translocation are determinant s of height (IGF2:11p15.5), red cell haemoglobinization (non-alpha glo bin gene complex: 11p15.5) and oncogenesis (cHa-Ras-1, Beckwith-Wiedem ann syndrome: 11p15.5; BCR, Burkitts lymphoma, Ewings sarcoma: 22q11.2 1). To map these regions in the patient, somatic cell hybrids were gen erated and cell lines that segregated the chromosomes 11, 22 and 22q- were obtained. All 11p15.5 sequences investigated, in particular the w hole of the non-alpha globin gene complex including its 5' and 3' regu latory sequences, were found to be translocated to 22q-. All chromosom e 22 sequences studied were missing from the 22q- cell lines, includin g the proximal anonymous marker D22S24, and therefore assumed to be tr anslocated to 11p+. These results suggest that the non-alpha globin ge ne complex has been moved close to the centromeric region of chromosom e 22q-. It is postulated that such a positioning subjects the complex to a variegated position-effect bringing about a clonal exclusion of t he complex and thus producing a beta-thalassaemia trait mosaic.