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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-5-4
pubmed:abstractText
Glycogen storage disease type II (GSDII), an autosomal recessive myopathic disorder, results from deficiency of lysosomal acid alpha-glucosidase. We searched for mutations in an evolutionarily conserved region in 54 patients of differing phenotype. Four novel mutations (D645N, G448S, R672W, and R672Q) and a previously described mutation (C647W) were identified in five patients and their deleterious effect on enzyme expression demonstrated in vitro. Two novel frame-shifting insertions/deletions (delta nt766-785/insC and +insG@nt2243) were identified in two patients with exon 14 mutations. The remaining three patients were either homozygous for their mutations (D645N/D645 and C647W/C647W) or carried a previously described leaky splice site mutation (IVS1-13T-->G). For all patients "in vivo" enzyme activity was consistent with clinical phenotype. Agreement of genotype with phenotype and in vitro versus in vivo enzyme was seen in three patients (two infantile patients carrying C647W/C647W and D645N/+insG@nt2243 and an adult patient heteroallelic for G648S/IVS1-13T-->G). Relative discordance was found in a juvenile patient homozygous for the non-expressing R672Q and an adult patient heterozygous for the minimally expressing R672W and delta nt766-785/+insC. Possible explanations include differences in in vitro assays vs in vivo enzyme activity, tissue specific expression with diminished enzyme expression/stability in fibroblasts vs muscle, somatic mosaicism, and modifying genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
244
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
921-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9535769-Adult, pubmed-meshheading:9535769-Child, Preschool, pubmed-meshheading:9535769-Female, pubmed-meshheading:9535769-Fibroblasts, pubmed-meshheading:9535769-Frameshift Mutation, pubmed-meshheading:9535769-Genotype, pubmed-meshheading:9535769-Glucan 1,4-alpha-Glucosidase, pubmed-meshheading:9535769-Glycogen Storage Disease Type II, pubmed-meshheading:9535769-Homozygote, pubmed-meshheading:9535769-Humans, pubmed-meshheading:9535769-Male, pubmed-meshheading:9535769-Middle Aged, pubmed-meshheading:9535769-Muscles, pubmed-meshheading:9535769-Mutagenesis, Site-Directed, pubmed-meshheading:9535769-Mutation, pubmed-meshheading:9535769-Phenotype, pubmed-meshheading:9535769-Sequence Analysis, DNA, pubmed-meshheading:9535769-Sequence Deletion, pubmed-meshheading:9535769-alpha-Glucosidases
pubmed:year
1998
pubmed:articleTitle
Glycogen storage disease type II: identification of four novel missense mutations (D645N, G648S, R672W, R672Q) and two insertions/deletions in the acid alpha-glucosidase locus of patients of differing phenotype.
pubmed:affiliation
Department of Medicine, NYU Med Center, New York 10016, USA.
pubmed:publicationType
Journal Article, Case Reports, Research Support, Non-U.S. Gov't