Dataset Information

The Identification of Pompe Disease Mutations in Archival Tissues and Development of a Rapid Molecular-based Test.

ABSTRACT:

Objectives

Pompe disease (glycogen storage disease type II) is a rare autosomal recessive lysosomal storage disease that is caused by acid alpha-glucosidase deficiency. Early enzyme replacement therapy can benefit infants with the disease but the diagnosis is complicated by the rarity of the disease and the heterogeneity of the clinical manifestations. In this study, DNA extracted from archival postmortem formalin-fixed paraffin-embedded tissues was used to identify Pompe disease mutations in Oman and develop a rapid molecular-based test.

Methods

Intronic primers were designed to amplify short fragments (193-454 base pairs [bp]) from coding exons (2-20) and screen for mutations using direct sequencing (DS).

Results

Two mutations known to cause severe disease were identified in two samples. One was a coding mutation, c.2560C>T (p.Arg854X), and the second was found at a splice acceptor site, c.1327-2A>G. Polymerase chain reaction- and restriction fragment length polymorphism-based tests were designed for the rapid genotyping of the identified mutations.

Conclusion

These tests can facilitate prenatal diagnosis and help in identifying carriers in families with the identified mutations.

SUBMITTER: Alansari A

PROVIDER: S-EPMC3836638 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Publications

The Identification of Pompe Disease Mutations in Archival Tissues and Development of a Rapid Molecular-based Test.

Alansari Aliya A Al-Rawahi Samira S Ba-Omar Taher T Al-Nabhani Mariam M Date Anand A

Sultan Qaboos University medical journal 20131108 4

<h4>Objectives</h4>Pompe disease (glycogen storage disease type II) is a rare autosomal recessive lysosomal storage disease that is caused by acid alpha-glucosidase deficiency. Early enzyme replacement therapy can benefit infants with the disease but the diagnosis is complicated by the rarity of the disease and the heterogeneity of the clinical manifestations. In this study, DNA extracted from archival postmortem formalin-fixed paraffin-embedded tissues was used to identify Pompe disease mutatio ...[more]

PMID: 24273659

Similar Datasets

Project description:BackgroundPompe disease (PD) is a rare, progressive, and autosomal recessive lysosomal storage disorder caused by mutations in the acid α-glucosidase gene. The clinical course and molecular mechanism of this disease in China have not been well defined.MethodsIn this single-center cohort study, we investigated a total of 15 Chinese patients with Pompe disease to better understand the clinical manifestations, echocardiographic imaging and genetic characteristics in this population.ResultsThe median age of 15 patients at symptom onset was 5.07 months (1-24 months). The median age at diagnosis was 19.53 months (range: 3 to 109 months, n = 15). Average diagnostic delay was 13.46 months. None of the patients had received enzyme replacement therapy (ERT). Fifteen patients died at a median age of 24.80 months due to cardiorespiratory failure (range 3-120 months). Myasthenia symptoms and severe hypertrophic cardiomyopathy were universally present (15/15 = 100%). Global longitudinal strain (GLS) by echocardiography was significantly lower in these patients. After adjusting for gender, body surface area (BSA), left ventricular ejection fraction (LVEF), E/e'ratio, maximum left ventricular wall thickness (MLVWT), left ventricular posterior wall (LVPW), left ventricular outflow tract (LVOT)gradient, GLS was independently correlated with survival time (hazard ratio (HR) = 0.702, 95% confidence Interval (CI): 0.532-0.925, P = 0.012). In our cohort, we identified 4 novel GAA mutation: c.2102T > C (p.L701P), c.2006C > T (p.P669l), c.766T > A (p.Y256N), c.2405G > T (p.G802V). 12 patients were compound heterozygotes, and 4 homozygotes.ConclusionsOur study provides a comprehensive examination of PD clinical course and mutations of the GAA gene for patients in China. We showed clinical utility of echocardiography in quantifying heart involvement in patients with suspected PD. GLS can provide prognostic information for mortality prediction. We reported four novel mutations in the GAA gene for the first time. Our findings may improve early recognition of PD characteristics in Chinese patients.

Dataset Information

The Identification of Pompe Disease Mutations in Archival Tissues and Development of a Rapid Molecular-based Test.

Objectives

Methods

Results

Conclusion

Publications

The Identification of Pompe Disease Mutations in Archival Tissues and Development of a Rapid Molecular-based Test.

Similar Datasets

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