The insertion of an L1 fragment within the IVS-II of the beta-globin gene results in a beta°-thal. This condition was observed in the mother and daughter of a Czech family who exhibited the clinical picture of beta-thal trait with microcytic anemia and elevated Hb A2. Restriction endonuclease analyses indicated a previously undescribed chromosomal rearrangement involving an insertion of 6-7 kb DNA into beta-IVS-II. Restriction mapping of the insertion was identical to an L1.2 transposon and showed the reverse orientation of the L1 element with respect to the beta-globin gene. Sequence analysis of the 3' end of the insertion (~600 bp) displayed 97% homology to the 5' terminal region of the L1.2 including 100% homology to the unique G/C rich promoter consensus sequence which initiates L1 transcription. The insertion breakpoint is located at the 3' end of beta-IVS-II within the "recombination region" previously identified to be a part of an ancestral L1 element. The parental target DNA sequence forms a 34 bp hairpin loop as well as a short palindrome and is homologous to a conserved transposonal heptanucleotide (ACGAAAA). The affected gene expresses full length beta-globin transcripts at the level corresponding to about 15% of total beta-globin mRNA. The L1 insertion within beta-IVS-II represents a new form of beta-thal.
|1.||Divoky, V., Mrug, M., Brabec, V., Indrak, K., Huisman, T.H.J., and Prchal, J.T.: Blood, 88:148a (Suppl. 1), 1996.|