A novel mutation has been identified in a patient with the Hunter syndrome (mucopolysaccharidosis type II), in whom the disorder is associated with two distinct deletions separated by 30 kb. The deletions were characterized by Southern blot and PCR analyses, and the nucleotide sequences at both junctions were determined. The first deletion, corresponding to a loss of 3152 bp of DNA, included exons 5 and 6 of the iduronate-2-sulfatase (IDS) gene. The second deletion was 3603 bp long and included exons 3 and 4 of gene W, which is located in the DXS466 locus telomeric of the IDS gene. Both deletions are the result of nonhomologous (illegitimate) recombination events between short direct repeats at the deletion breakpoints. An interesting finding was the presence of the heptamer sequence 5'-TACTCTA-3' present at both deletion junctions, suggesting that this motif might be a hot spot for recombination. We propose that the double deletion is the result of homology-associated nonhomologous recombinations caused by the presence of large duplicated regions in Xq27.3-q28.

dx.doi.org/10.1006/geno.1997.4811, hdl.handle.net/1765/58760
Department of Clinical Genetics

Karsten, S.L, Lagerstedt, K, Carlberg, C, Kleijer, W.J, Zaremba, R, van Diggelen, O.P, … Bondeson, M.-L. (1997). Two distinct deletions in the IDS gene and the gene W: A novel type of mutation associated with the hunter syndrome. Genomics, 43(2), 123–129. doi:10.1006/geno.1997.4811