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Twenty‐two novel mutations in the lysosomal α‐glucosidase gene ( GAA ) underscore the genotype–phenotype correlation in glycogen storage disease type II
Author(s) -
Hermans Monique M.P.,
Leenen Dik van,
Kroos Marian A.,
Beesley Clare E.,
Van der Ploeg Ans T.,
Sakuraba Hitoshi,
Wevers Ron,
Kleijer Wim,
Michelakakis Helen,
Kirk Edwin P.,
Fletcher Janice,
Bosshard Nils,
BaselVanagaite Lina,
Besley Guy,
Reuser Arnold J.J.
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10286
Subject(s) - glycogen storage disease type ii , biology , missense mutation , genetics , phenotype , genotype , gene , allele , mutation , glycogen storage disease , lysosomal storage disease , genotype phenotype distinction , disease , microbiology and biotechnology , glycogen , enzyme , medicine , endocrinology , biochemistry , enzyme replacement therapy
Patients with glycogen storage disease type II (GSDII, Pompe disease) suffer from progressive muscle weakness due to acid α‐glucosidase deficiency. The disease is inherited as an autosomal recessive trait with a spectrum of clinical phenotypes. We have investigated 29 cases of GSDII and thereby identified 55 pathogenic mutations of the acid α‐glucosidase gene ( GAA ) encoding acid maltase. There were 34 different mutations identified, 22 of which were novel. All of the missense mutations and two other mutations with an unpredictable effect on acid α‐glucosidase synthesis and function were transiently expressed in COS cells. The effect of a novel splice‐site mutation was investigated by real‐time PCR analysis. The outcome of our analysis underscores the notion that the clinical phenotype of GSDII is largely dictated by the nature of the mutations in the GAA alleles. This genotype–phenotype correlation makes DNA analysis a valuable tool to help predict the clinical course of the disease. Hum Mutat 23:47–56, 2004. © 2003 Wiley‐Liss, Inc.