Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II

A. L E Montalvo, B. Bembi, M. Donnarumma, M. Filocamo, G. Parenti, M. Rossi, L. Merlini, E. Buratti, P. De Filippi, A. Dardis, M. Stroppiano, G. Ciana, Maria Gabriela Pittis

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Abstract

Glycogen storage disease type II (GSDII) is a recessively inherited disorder due to the deficiency of acid α-glucosidase (GAA) that results in impaired glycogen degradation and its accumulation in the lysosomes. We report here the complete molecular analysis of the GAA gene performed on 40 Italian patients with late onset GSDII. Twelve novel alleles have been identified: missense mutations were functionally characterized by enzyme activity and protein processing in a human GAA-deficient cell line while splicing mutations were studied by RT-PCR and in silico analysis. A complex allele was also identified carrying three different alterations in cis. The c.-32-13T>G was the most frequent mutation, present as compound heterozygote in 85% of the patients (allele frequency 42.3%), as described in other late onset GSDII Caucasian populations. Interestingly, the c.-32-13T>G was associated with the c.2237G>A (p.W746X) in nine of the 40 patients. Genotype-phenotype correlations are discussed with particular emphasis on the subgroup carrying the C.-32-13T>G/c.2237G>A genotype.

Original languageEnglish
Pages (from-to)999-1006
Number of pages8
JournalHuman Mutation
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 2006

Fingerprint

Glycogen Storage Disease Type II
Mutation
Alleles
Glucosidases
Genes
Genetic Association Studies
Missense Mutation
Heterozygote
Lysosomes
Glycogen
Gene Frequency
Computer Simulation
Genotype
Cell Line
Polymerase Chain Reaction
Acids
Enzymes
Population
Proteins

Keywords

  • Acid α-glucosidase
  • Acid maltase
  • GAA
  • Glycogen storage disease type II
  • Late onset
  • Pompe disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Montalvo, A. L. E., Bembi, B., Donnarumma, M., Filocamo, M., Parenti, G., Rossi, M., ... Pittis, M. G. (2006). Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II. Human Mutation, 27(10), 999-1006. https://doi.org/10.1002/humu.20374

Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II. / Montalvo, A. L E; Bembi, B.; Donnarumma, M.; Filocamo, M.; Parenti, G.; Rossi, M.; Merlini, L.; Buratti, E.; De Filippi, P.; Dardis, A.; Stroppiano, M.; Ciana, G.; Pittis, Maria Gabriela.

In: Human Mutation, Vol. 27, No. 10, 10.2006, p. 999-1006.

Research output: Contribution to journalArticle

Montalvo, ALE, Bembi, B, Donnarumma, M, Filocamo, M, Parenti, G, Rossi, M, Merlini, L, Buratti, E, De Filippi, P, Dardis, A, Stroppiano, M, Ciana, G & Pittis, MG 2006, 'Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II', Human Mutation, vol. 27, no. 10, pp. 999-1006. https://doi.org/10.1002/humu.20374
Montalvo, A. L E ; Bembi, B. ; Donnarumma, M. ; Filocamo, M. ; Parenti, G. ; Rossi, M. ; Merlini, L. ; Buratti, E. ; De Filippi, P. ; Dardis, A. ; Stroppiano, M. ; Ciana, G. ; Pittis, Maria Gabriela. / Mutation profile of the GAA gene in 40 Italian patients with late onset glycogen storage disease type II. In: Human Mutation. 2006 ; Vol. 27, No. 10. pp. 999-1006.
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