title: Genotype-phenotype correlation in Pompe disease, a step forward.
abstract: BACKGROUND
  Pompe's disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family.
  
  
  METHODS
  For a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase. DNA was extracted and tested for GAA mutations and some genetic polymorphisms able to influence muscle properties (ACE, ACTN3, AGT and PPARα genes).We compared the polymorphisms analyzed in groups of patients with Pompe disease clustered for their homogeneous genotype.
  
  
  RESULTS
  We have been able to identify four subgroups of patients completely homogeneous for their genotype, and two groups homogeneous as far as the second mutation is defined "very severe" or "potentially less severe". When disease free life was studied we observed a high significant difference between groups. The DD genotype in the ACE gene and the XX genotype in the ACTN3 gene were significantly associated to an earlier age of onset of the disease. The ACE DD genotype was also associated to the presence of muscle pain.
  
  
  CONCLUSIONS
  We demonstrate that ACE and ACTN3 polymorphisms are genetic factors able to modulate the clinical phenotype of patients affected with Pompe disease.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy. paola.defilippi@unipv.it.
authors.forename: Paola
authors.initials: P
authors.lastname: De Filippi
authors.forename: Kolsoum
authors.initials: K
authors.lastname: Saeidi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ravaglia
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.forename: Corrado
authors.initials: C
authors.lastname: Angelini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mongini
authors.forename: Lucia
authors.initials: L
authors.lastname: Morandi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Muzio
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
authors.forename: Fabio
authors.initials: F
authors.lastname: Giannini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marrosu
authors.forename: Miriam
authors.initials: M
authors.lastname: Rigoldi
authors.forename: Paola
authors.initials: P
authors.lastname: Tonin
authors.forename: Serenella
authors.initials: S
authors.lastname: Servidei
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Annalisa
authors.initials: A
authors.lastname: Carlucci
authors.forename: Claudia
authors.initials: C
authors.lastname: Scotti
authors.forename: Mario
authors.initials: M
authors.lastname: Comelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Toscano
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
mesh_terms: D000185:Actinin / Q000235:genetics; D000808:Angiotensinogen / Q000235:genetics; D005838:Genotype; D006009:Glycogen Storage Disease Type II / Q000235:genetics* / Q000503:physiopathology*; D006801:Humans; D009154:Mutation; D047493:PPAR alpha / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype
chemical_list: C118456:ACTN3 protein, human; C534931:AGT protein, human; D047493:PPAR alpha; D000808:Angiotensinogen; D000185:Actinin; D007703:Peptidyl-Dipeptidase A
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