We identified the presumably rare event of de novo mutation in an autosomal recessive disorder, glycogen storage disease type II (GSDII). GSDII results from inherited deficiency of acid alpha-glucosidase (acid maltase) and both the expressed and structural gene (designated GAA) have been isolated. The mutation was a deletion of 13 nt of coding sequence (delta nt 1456-1468) on the paternally derived allele of the proband. The delta nt 1456-1468 results in a reading frameshift and a premature termination signal upstream of the enzyme catalytic site. Paternity was confirmed by presence of two downstream, uncommon amino acid substitutions (E689K, W746C) in both proband and father and by comparison of nine short tandem repeats. The maternal allele carried a newly identified deleterious C647W missense mutation in a highly conserved area of the protein. The C647W mutation was also found in a second unrelated proband, heteroallelic with a deletion extending from IVS17 to IVS18.

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