Identification of the first deletion-insertion involving the complete structure of GAA gene and part of CCDC40 gene mediated by an Alu element

Gene. 2013 Apr 25;519(1):169-72. doi: 10.1016/j.gene.2013.01.051. Epub 2013 Feb 9.

Abstract

Pompe disease is an uncommon autosomal recessive glycogen storage disorder caused by deficiency of acid α-glucosidase. Classic infantile form triggers severe cardiomyopathy, hypotonia, and respiratory failure, leading to death within the first two years of life. The majority of patients with Pompe disease have been reported to have point mutations in the GAA gene. We report the first complex deletion-insertion encompassing the complete structure of GAA gene and a large fragment of the gene CCDC40 in a patient with very severe form of Pompe disease. Sequencing analysis of breakpoints allowed us to determine the potential implication of an Alu repeat in the pathogenic mechanism. We suggest that molecular strategy of Pompe disease should include systematic analysis of large rearrangements.

Publication types

  • Case Reports

MeSH terms

  • Alu Elements*
  • Base Sequence
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Genome, Human
  • Glucan 1,4-alpha-Glucosidase / deficiency
  • Glucan 1,4-alpha-Glucosidase / genetics
  • Glycogen Storage Disease Type II / genetics
  • Glycogen Storage Disease Type II / pathology
  • Humans
  • Infant, Newborn
  • Male
  • Microarray Analysis
  • Molecular Sequence Data
  • Nucleic Acid Amplification Techniques
  • Proteins / genetics*
  • Proteins / metabolism
  • Respiratory Insufficiency / genetics
  • Respiratory Insufficiency / pathology
  • Sequence Analysis, DNA
  • Spain
  • White People / genetics
  • alpha-Glucosidases / genetics*
  • alpha-Glucosidases / metabolism

Substances

  • CCDC40 protein, human
  • Proteins
  • GAA protein, human
  • alpha-Glucosidases
  • Glucan 1,4-alpha-Glucosidase