IDENTIFICATION OF A MUTATION IN THE STRUCTURAL ALPHA-L-FUCOSIDASE GENE IN FUCOSIDOSIS

  • 1 November 1988
    • journal article
    • research article
    • Vol. 43  (5) , 756-763
Abstract
Fucosidosis is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration and mental retardation. The disease results from deficient activity of .alpha.-L-fucosidase (E.C.3.2.1.51), a lysosomal enzyme that hydrolyzes fucose from fucoglycoconjugates. In an attempt to identify the mutation(s) and result(s) in fucosidosis, we performed Southern blot analysis of the structural gene encoding .alpha.-L-fucosidase (FUCA 1) in 23 patients affected with fucosidosis. In five patients Southern blot analysis showed obliteration of an EcoRI restriction site in the open reading frame of FUCA 1 encoding mature .alpha.-L-fucosidase. This abnormality was not observed in 80 controls, and it may be the basic defect responsible for fucosidase. This abnormality was not observed in 80 controls, and it may be the basic defect responsible for fucosidosis in these patients. Both patients with the severe type I form of fucosidosis and patients with the less severe type II were shown to be homozygous for this presumed mutation. In the remaining 18 patients the EcoRI site obliteration, major-gene deletions, or insertions were not detected. This suggests that at least two different mutations are involved in fucosidosis. The heterogeneity found at the DNA level was not present at the protein level, as all fucosidosis patients investigated had low fucosidase protein (< 6% of normal) and negligible fucosidase activity in fibroblasts and lymphoblastoid cell lines.