Journal of Neurology

, Volume 255, Issue 6, pp 831–838 | Cite as

Identification of eight novel mutations of the acid α-glucosidase gene causing the infantile or juvenile form of glycogen storage disease type II

  • L. Wan
  • C.-C. Lee
  • C.-M. Hsu
  • W.-L. Hwu
  • C.-C. Yang
  • C.-H. Tsai
  • F.-J. Tsai
ORIGINAL COMMUNICATION
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Abstract

Glycogen-storage disease type II (GSDII; OMIM #232300), an autosomal recessive disorder caused by a deficiency of the glycogen hydrolysis enzyme acid α-glucosidase (acid GAA; acid maltase, EC. 3.2.10.20), results in the accumulation of glycogen in the lysosome. We performed a molecular genetic study on 29 patients with infantile-onset glycogen-storage disease type II (GSDII), 6 with juvenile-onset GSDII and one carrier for GSDII. Seventeen different mutations were identified among them; 8 were novel mutations: c.421C > A (p.L141M), c.872T > C (p.L291P), c.893A > C (p.Y298S), c.1375G > A (p.D459N), c.1437G > C (p.K479N), c.1509_1511del (p.A504del), c.1960T > C (p.S654P), and c.2174G > C (p.R725P). One of the mutations identified, c.2238G > C (p.W746C), which was a sequence change of unknown pathogenic significance causing diminished enzyme activity,was found homozygously in a juvenile-onset patient. We also found a juvenile-onset patient with homozygote c.1935C > A mutation which was frequently found in infantile-onset patients. In addition to mutations, we also identified 14 new polymorphisms in the acid α-glucosidase gene. The genotype/phenotype correlations indicated that c.2238G > C (p.W746C) is correlated with juvenile- onset GSDII and that c.872T > C (p.L291P) and c.1411_1414del (p.E471fsX5) are correlated with infantile-onset GSDII. Mutational analysis of GAA is useful in genetic counseling and prenatal diagnosis of the disease.

Key words

glycogen storage disease type II Pompe disease acid α-glucosidase novel mutation mutation analysis 
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Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • L. Wan
    • 1
    • 2
    • 3
  • C.-C. Lee
    • 1
  • C.-M. Hsu
    • 1
  • W.-L. Hwu
    • 4
  • C.-C. Yang
    • 5
  • C.-H. Tsai
    • 1
    • 3
  • F.-J. Tsai
    • 1
    • 2
    • 3
  1. 1.Dept. of Medical Genetics and Medical, ResearchChina Medical University HospitalTaichungTaiwan
  2. 2.Graduate Institute of Chinese Medical ScienceChina Medical UniversityTaichungTaiwan
  3. 3.Dept. of Biotechnology and BioinformaticsAsia UniversityTaichungTaiwan
  4. 4.Dept. of Pediatrics and Medical GeneticsNational Taiwan University HospitalTaipeiTaiwan
  5. 5.Dept. of NeurologyNational Taiwan University HospitalTaipeiTaiwan

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