Identification of a de novo point mutation resulting in infantile form of Pompe's disease.

One patient in a nonconsanguineous Taiwanese family with infantile glycogen storage disease type II (Pompe's) disease was found to have a de novo mutation of G1933 to C transition [corrected] in exon 14 of the human lysosomal alpha-D-glucosidase gene. Patient was homozygous and both parents were heterozygous for the mutant allele. The mutation caused an Asp to His substitution at amino acid position 645. The mutation was introduced in wild type lysosomal alpha-D-glucosidase cDNA and the mutant construct was expressed in vivo. The Glu to His substitution was proven to cause significant loss of enzyme activity. In homozygous form it leads to the severe infantile phenotype of Pompe's disease.