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Dutch patients with glycogen storage disease type II show common ancestry for the 525delT and del exon 18 mutations
  1. Margreet G E M Ausemsa,
  2. Klara ten Berga,
  3. Lodewijk A Sandkuijla,b,
  4. Marian A Kroosb,
  5. Alfons F J Bardoela,
  6. Katerina N Roumeliotia,
  7. Arnold J J Reuserb,
  8. Richard Sinkea,
  9. Cisca Wijmengaa
  1. aDepartment of Medical Genetics, University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands, bDepartment of Clinical Genetics, Erasmus University, Academic Hospital Rotterdam, The Netherlands
  1. Dr Ausems,M.G.E.M.Ausems{at}

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Editor—Glycogen storage disease type II (GSD II) is an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase. The enzyme deficiency results in intralysosomal accumulation of glycogen in skeletal muscle and in other tissues. There are early and late onset phenotypes which differ with respect to age at onset, extent of organ involvement, and clinical course of the disease.1 The genotype frequency of GSD II was recently shown to be 1 in 40 000 by mutation screening in the general population, which is higher than previously estimated.2 3

Over 40 different mutations in the acid α-glucosidase (GAA) gene have been reported.4 Most mutations are rare and have been found in only a few patients. However, some mutations have been reported in several unrelated patients with defined ethnic origins. The C1935A transversion, frequently found in Chinese patients with infantile GSD II, appears to originate from a common founder.5 Other frequent mutations include the R854X mutation in Afro-Americans,6 the 2741AG→CAGG insertion in Turkish patients,7 and the G925A mutation in European patients.8 It remains to be determined whether these frequent mutations represent common descent or result from independent recurrence. The IVS1(−13T→G) mutation is the most frequent mutation in late onset GSD II patients from different ethnic origins.9-11

In The Netherlands, most late onset GSD II patients carry the IVS1(−13T→G) mutation in combination with either the 525delT or the del exon 18 mutation, whereas infantile GSD II patients often show homozygosity or compound heterozygosity for the 525delT and the del exon 18 mutations.10 The latter mutations are fully deleterious and are associated with complete loss of enzyme activity.12 13 The deletion of exon 18 extends from IVS17 to IVS18 and includes the coding sequence of exon 18. Analysis of the deletion junction …

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