Splicing Mutations in Glycogen-storage Disease Type II: Evaluation of the Full Spectrum of Mutations and Their Relation to Patients' Phenotypes

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2010 Dec 24

PMID 21179066

Citations 16

Authors

Stefania Zampieri

Emanuele Buratti

Silvia Dominissini

Anna Lisa Montalvo

Maria Gabriela Pittis

Bruno Bembi

Andrea Dardis

Affiliations

Soon will be listed here.

Abstract

Glycogen-storage disease type II is an autosomal recessive-inherited disorder due to the deficiency of acid α-glucosidase. A large number of mutations in the acid α-glucosidase gene have been described to date. Among them, ~15% are variations that may affect mRNA splicing process. In this study, we have for the first time comprehensively reviewed the available information on splicing mutations of the acid α-glucosidase gene and we have evaluated their possible impact on the splicing process using different in silico approaches. Out of the 39 different GAA-sequence variations described, an in silico analysis using seven different programs showed that 97% of them are predicted to have an impact on the splicing process. Moreover, this analysis showed a quite good correlation between the impact of the mutation on the splicing process and the clinical phenotype. In addition, we have performed the functional characterization of three novel sequence variants found in Italian patients and still uncharacterized. Using a minigene system, we have confirmed their pathogenic nature. In conclusion, this study has shown that in silico analysis represents a useful tool to select mutations that affect the splicing process of the acid α-glucosidase gene and provides an updated picture of all this kind of mutations reported till now.

Citing Articles

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