Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen storage disease type Ia

Research output: Contribution to journalArticle

Abstract

Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7% of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80% of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalJournal of Inherited Metabolic Disease
Volume22
Issue number1
DOIs
Publication statusPublished - 1999

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Glycogen Storage Disease
Glucose-6-Phosphatase
Mutation
Genes
Alleles
Glycogen Storage Disease Type I
Sicily
Single-Stranded Conformational Polymorphism
Prenatal Diagnosis
DNA Sequence Analysis
Organism Cloning
Biopsy
Liver
DNA

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

Cite this

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title = "Mutations in the glucose-6-phosphatase gene of 53 Italian patients with glycogen storage disease type Ia",
abstract = "Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9{\%} of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7{\%} of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80{\%} of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.",
author = "M. Stroppiano and S. Regis and M. DiRocco and F. Caroli and P. Gandullia and R. Gatti",
year = "1999",
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AU - Stroppiano, M.

AU - Regis, S.

AU - DiRocco, M.

AU - Caroli, F.

AU - Gandullia, P.

AU - Gatti, R.

PY - 1999

Y1 - 1999

N2 - Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7% of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80% of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.

AB - Type Ia glycogen storage disease (GSD1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Recent cloning of the G6Pase gene and the subsequent identification of several disease-causing mutations have shown an ethnic molecular heterogeneity. Using SSCP analysis and DNA sequencing, we characterized the G6Pase gene of 53 unrelated Italian patients. The two most common mutations, R83C and Q347X, accounted for 66.9% of the mutant alleles. Eight novel mutations and three rare mutations were identified in 15.7% of disease alleles. These results suggest that a DNA-based method can be used as an initial screening in Italian patients clinically suspected of having GSD1a, avoiding liver biopsy for enzymatic diagnosis. In particular, a noninvasive diagnosis is a suitable method for the Italian subpopulation coming from Sicily, where the R83C mutation is present in 80% of mutant alleles. Molecular carrier detection and prenatal diagnosis can be provided to GSD1a families with identified mutation in the propositus.

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