In addition to local sequence elements the regulation of the high-level, 
development- and tissue-specific expression of the human beta globin gene 
cluster appears to require distant regulatory sequences which have been termed 
locus control region. In the chromatin of erythroid cells the locus control 
region is characterized by four DNaseI hypersensitive sites that are located 
6-18 kb 5' of the epsilon globin gene. The definition of the sequences minimally 
required for locus control region activity is likely to further the 
understanding of its physiology and will be of interest for the development of 
somatic gene therapy strategies of the hemoglobinopathies. We present here the 
analysis of a family with a 3,030-bp deletion of sequences upstream of the 
epsilon globin gene including the most 3' locus control region element and 
cosegregating beta(0) thalassemia. The deletion is linked in cis to a 
structurally and functionally normal beta globin gene. The proximal element of 
the locus control region does not therefore appear to be necessary for beta 
globin gene activity in vivo.