Fucosidosis is an autosomal recessive
lysosomal storage disease resulting from absence of
alpha-L-fucosidase activity. Lymphoid cell lines from two siblings with
fucosidosis and a healthy individual (control) had
alpha-L-fucosidase mRNA of normal size (2.3 kb) but the level of
alpha-L-fucosidase mRNA in the patients' cells was reduced.
cDNA was prepared and amplified from
alpha-L-fucosidase mRNA of lymphoid cells of the patients, their carrier parents, and the control. Direct
DNA sequencing demonstrated three mutations in the
fucosidosis family. One mutation, C1282-->T, changed the
codon (CAA) for Gln-422 to a
stop codon (UAA). This mutation was heterozygous (C and T) in the patients and their father and independently confirms an earlier report (J. Mol. Neurosci. (1989) 1, 177). Another mutation, C247-->T, changed the
codon (CAG) for Gln-77 to a
stop codon (UAG) and was heterozygous (C and T) in the patients and their mother. The third mutation, A860-->G, changed the
codon CAG for Gln-281 to the
codon (CGG) for Arg and was heterozygous (A and G) in the patients but homozygous in their father.
alpha-L-Fucosidase activity in cells of the father was 37% of controls indicating that homozygosity of the A860-->G mutation did not cause an absence of
alpha-L-fucosidase activity and
fucosidosis. This mutation probably results in a normal polymorphic variant of
alpha-L-fucosidase. It is proposed that the combination of the C247-->T mutation on the maternal allele of the
alpha-L-fucosidase gene and the C1282-->T mutation on the paternal allele caused
fucosidosis in the patients.