Frequent deletions of the human X chromosome distal short arm result from recombination between low copy repetitive elements

Substantial DNA deletions appear to be the molecular basis of several human genetic disorders but rarely account for the majority of observed mutations at any given locus. Exceptions in which deletions do account for the majority of observed abnormalities include the alpha-thalassemias, Duchenne muscular dystrophy, and steroid sulfatase deficiency. Variable deletion breakpoints have been recognized at the alpha-globin and dystrophin loci, but no information is available regarding STS deletions. We have found that these STS alterations usually involve breakpoints within highly similar sequence elements situated approximately 1.9 megabases apart on the X chromosome. It is surprising that these very large deletions produce such mild clinical abnormalities. These results may provide insight into the molecular mechanism of a number of human genetic defects.