© 1994 Oxford University Press
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The effect of a single base pair deletion (
T525) and a C1634T missense mutation (pro545leu) on the expression of lysosomal 
-glucosidase in patients with glycogen storage disease type II
Department of Clinical Genetics, Erasmus University PO Box 1738, 3000 DR Rotterdam, the Netherlands
*To whom correspondence should be addressed
Received August 18, 1994; Accepted September 23, 1994
Glycogen storage disease type II (GSDII, Pompe's disease) is caused by an autosomal recessive inheritance of lysosomal 
-glucosldase deficiency. By sequence analysis we have identified the mutations in the lysosomal -glucosldase gene (GAA) of two unrelated patients, who have one and two copies, respectively, of the same mlssense mutation. The milder affected adult patient was found to be homozygous for a C1634T transition resulting in the substitution of pro545 by leu. The more severely affected adolescent patient had this same mutant allele combined with a 1 base pair deletion (AT525) In the second allele causing premature termination at nucleotlde positions 658–660. Both these mutations were Introduced in wild-type -glucosldase cDNA and expressed In COS-1 cells to analyse their effect. The 
T525 mutation prohibits the formation of lysosomal -glucosldase completely. The pro545-leu substitution Is compatible with normal synthesis but hampers enzyme maturation and results In a 92% net loss of lysosomal -glucosidase activity. The patient with adult GSDII has, In accordance with the allellc constitution, a 2-fold higher residual activity than the patient with juvenile GSDII. The T525 deletion was detected In two other unrelated patients, and also the C1634T transition was encountered in two more Caucasian patients with GSDII.
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