Mutation profile of theGAA gene in 40 Italian patients with late onset glycogen storage disease type II
- 29 August 2006
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 27 (10), 999-1006
- https://doi.org/10.1002/humu.20374
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. Hum Mutat 27(10), 999–1006, 2006.This publication has 37 references indexed in Scilit:
- Pompe disease in infants and childrenThe Journal of Pediatrics, 2004
- Glycogenosis type II: identification and expression of three novel mutations in the acid α-glucosidase gene causing the infantile form of the diseaseMolecular Genetics and Metabolism, 2004
- Maximum Entropy Modeling of Short Sequence Motifs with Applications to RNA Splicing SignalsJournal of Computational Biology, 2004
- Twenty-two novel mutations in the lysosomal ?-glucosidase gene (GAA) underscore the genotype-phenotype correlation in glycogen storage disease type IIHuman Mutation, 2003
- Glycogen storage disease type II: identification of a dinucleotide deletion and a common missense mutation in the lysosomal α‐glucosidase geneClinical Genetics, 1998
- Glycogen Storage Disease Type II: Identification of Four Novel Missense Mutations (D645N, G648S, R672W, R672Q) and Two Insertions/Deletions in the Acid α-Glucosidase Locus of Patients of Differing PhenotypeBiochemical and Biophysical Research Communications, 1998
- Mutation Detection in Glycogen Storage Disease Type II by RT-PCR and Automated SequencingBiochemical and Biophysical Research Communications, 1997
- Improved Splice Site Detection in GenieJournal of Computational Biology, 1997
- The effect of a single base pair deletion (ΔT525) and a C1634T missense mutation (pro545leu) on the expression of lysosomal α-glucosidase in patients with glycogen storage disease type IIHuman Molecular Genetics, 1994
- A de novo 13 nt deletion, a newly identified C647W missense mutation and a deletion of exon 18 in infantile onset glycogen storage disease type II (GSDII)Human Molecular Genetics, 1994