TY - JOUR
T1 - Aberrant splicing in adult onset glycogen storage disease type II (GSDII)
T2 - Molecular identification of an IVS1 (- 13T→G) mutation in a majority of patients and a novel IVS10 (+ 1GT → CT) mutation
AU - Hule, M. L.
AU - Chen, A. S.
AU - Tsujino, S.
AU - Shanske, S.
AU - Dimauro, S.
AU - Engel, A. G.
AU - Hirschhorn, R.
N1 - Funding Information:
The authors are grateful to Dr K.Hirschhorn for establishing cell lines and his insightful discussions, Dr S.Tzall for performing S! nuclease analysis, Dr M.Yoder for assistence in preparing figures, and Drs Brown and Natowicz for GM11660 and GM11661 cell lines. This work was supported by a grant from the March of Dimes Birth Defects Foundation.
PY - 1994/12
Y1 - 1994/12
N2 - 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.
AB - 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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U2 - 10.1093/hmg/3.12.2231
DO - 10.1093/hmg/3.12.2231
M3 - Article
C2 - 7881425
AN - SCOPUS:0028593843
SN - 0964-6906
VL - 3
SP - 2231
EP - 2236
JO - Human molecular genetics
JF - Human molecular genetics
IS - 12
ER -