© 1994 Oxford University Press
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Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (– 13T
G) mutation in a majority of patients and a novel IVS10 (+ 1GT CT) mutation
New York University Medical Center, Department of Medicine, Division of Medical Genetics 550 First Avenue, New York, NY 10016 1Columbia College of Physicians & Surgeons, Department of Neurology 630 West 168th Street, New York, NY 10032 2Mayo Clinic Guggenheim Building, Rochester, MN 55905, USA
*To whom correspondence should be addressed
Received September 20, 1994; Revised October 10, 1994; Accepted October 10, 1994
Two newly identified splice site mutations (IVS1 – 13T 
G and IVS10 + 1GT CT) were found In a patient with adult onset of the autosomal recessive disorder glycogen storage disease type II (GSDII). The IVS1 – 13T G transverslon In the acceptor splice site was found on one allele In over two thirds of adult onset GSDII patients studied (28/41), but was not seen In 58 normal or 12 infantile onset GSDII chromosomes. Molecular analysis of cDNA from the Index patient and four additional, ethnically different, individuals carrying the IVS1 – 13T G transverslon showed splicing out of the first coding exon as well as rare utilization of a cryptic splice site in the exon. An IVS10 + 1GT CT transversion, unique to the index patient, was detected on the second chromosome. The IVS10 + 1GT CT results in splicing out of exon 10 including part of the enzyme catalytic site. Additionally, a large deletion encompassing exon 18, previously described In four unrelated patients, was also detected In three unrelated adult GSDII patients, two of whom carried the IVS1 –13T G transversion. The frequency of the IVS1 splice site mutation suggests that detection of this mutation could potentially aid in the diagnosis of the phenotypically variable syndrome of adult onset GSDII. The finding that the –13T G mutation Is a very common mutation in adult onset GSDII patients of varying ethnic and racial backgrounds, suggests that It is either an ancient mutation or confers a selective advantage. Although to our knowledge these are the first splice site mutations to be reported for GSDII, additional splice site mutations are likely and could provide the basis for later onset disease in GSDII.
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