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Open Access 01-12-2014 | Research

Genotype-phenotype correlation in Pompe disease, a step forward

Authors: Paola De Filippi, Kolsoum Saeidi, Sabrina Ravaglia, Andrea Dardis, Corrado Angelini, Tiziana Mongini, Lucia Morandi, Maurizio Moggio, Antonio Di Muzio, Massimiliano Filosto, Bruno Bembi, Fabio Giannini, Giovanni Marrosu, Miriam Rigoldi, Paola Tonin, Serenella Servidei, Gabriele Siciliano, Annalisa Carlucci, Claudia Scotti, Mario Comelli, Antonio Toscano, Cesare Danesino

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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.

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Title: Genotype-phenotype correlation in Pompe disease, a step forward
Authors: Paola De Filippi
Kolsoum Saeidi
Sabrina Ravaglia
Andrea Dardis
Corrado Angelini
Tiziana Mongini
Lucia Morandi
Maurizio Moggio
Antonio Di Muzio
Massimiliano Filosto
Bruno Bembi
Fabio Giannini
Giovanni Marrosu
Miriam Rigoldi
Paola Tonin
Serenella Servidei
Gabriele Siciliano
Annalisa Carlucci
Claudia Scotti
Mario Comelli
Antonio Toscano
Cesare Danesino
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-014-0102-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genotype-phenotype correlation in Pompe disease, a step forward

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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