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Identification of four novel mutations in the alpha glucosidase gene in five Italian patients with infantile onset glycogen storage disease type II
Author(s) -
Pittis Maria Gabriela,
Montalvo Anna Lisa E.,
Miocic Snjezana,
Martini Cristina,
Deganuto Marta,
Candusso Manila,
Ciana Giovanni,
Bembi Bruno
Publication year - 2003
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.20164
Subject(s) - glycogen storage disease type ii , point mutation , loss of heterozygosity , biology , mutation , allele , microbiology and biotechnology , compound heterozygosity , gene , glycogen storage disease , enzyme , stop codon , genetics , endocrinology , disease , medicine , glycogen , biochemistry , enzyme replacement therapy
Abstract Glycogen storage disease type II (GSDII) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme acid alpha glucosidase. Four novel mutations (C670T, G989A, G2188T, and Δ 23 nt 828‐850) were identified in five Italian patients with the infantile form of the disease. The C670T mutation was present in two unrelated patients in heterozygosity; the effect on enzyme activity was assessed by in vitro expression. COS‐1 cells expressing the C670T allele had a twofold higher activity than the negative control cells. The G989A and G2188T point mutations lead to the introduction of premature stop signals that results in truncated forms of alpha glucosidase. The in vitro expression of G2188T allele demonstrated no increment in activity compared to negative control. The frame shifting deletion of nucleotides 828–850 was identified in one patient in heterozygosity. The shift in the reading frame introduces a stop codon 135 nucleotides downstream the deletion junction that results in a truncated protein without catalytic activity. Nested PCR screening showed that the mutation was carried by the mother and was absent in the other members of the family. The four novel severe mutations herein described concerned only infantile onset GSDII patients; the loss of enzyme activity is correlated with the severity of the disease. © 2003 Wiley‐Liss, Inc.