DISTRIBUTION AND CHARACTERIZATION OF A SANDHOFF DISEASE-ASSOCIATED 50-KB DELETION IN THE GENE ENCODING THE HUMAN BETA-HEXOSAMINIDASE BETA-CHAIN

A 50-kb deletion was demonstrated in the gene encoding for the β-subunit of human hexosaminidase (HEXB), using field inversion gel electrophoresis (FIGE) of SfiI-digested chromosomal DNA from patients with Sandhoff disease. We investigated 14 patients from different parts of Europe and found no deletion in 5 patients, 2 patients homozygous for the deletion, and 7 patients with the deletion in one allele. The distribution of the 50-kb deletion was approximately in agreement with the Hardy-Weinberg equilibrium. The deletion was characterized using chromosomal DNA from one of the two homozygous patients. Restriction fragments were hybridized with a 1.6-kb (almost complete) and a 0.4-kb (5′) HEXB cDNA clone. It appeared that the deletion started in intron 5, extending in the 5′ direction and causing the loss of exon 1-5 and the promoter area of the HEXB gene. © 1990 Springer-Verlag.