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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1995 Apr;56(4):887–897.

Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II.

C F Boerkoel 1, R Exelbert 1, C Nicastri 1, R C Nichols 1, F W Miller 1, P H Plotz 1, N Raben 1
PMCID: PMC1801206  PMID: 7717400

Abstract

An autosomal recessive deficiency of acid alpha-glucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients--two infants and an adult--provided a rare opportunity to analyze the effect of the second mutation in patients who displayed dramatically different phenotypes. A deletion of Lys-903 in one patient and a substitution of Arg for Leu-299 in another resulted in the fatal infantile form. In the adult, a T-to-G base change at position -13 of intron 1 resulted in alternatively spliced transcripts with deletion of exon 2, the location of the start codon. The low level of active enzyme (12% of normal) generated from the leakage of normally spliced mRNA sustained the patient to adult life.

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