Two novel mutations in acid α-glucosidase gene in two patients with Pompe disease

Area of Science:

• Genetics
• Biochemistry
• Rare Diseases

Background:

• Pompe disease, or glycogen storage disease type II (GSD II), is an autosomal recessive lysosomal disorder.
• It results from deficiency of the enzyme acid alpha-glucosidase (GAA).
• The disease exhibits a wide range of genetic and clinical presentations, with infantile-onset Pompe disease being the most severe.

Observation:

• Infantile-onset Pompe disease is the most severe form, characterized by hypotonia and cardiomyopathy presenting early in infancy.
• Two families with Pompe disease were investigated, including probands who unfortunately died and were diagnosed with GSD type II.
• Molecular analysis of the parents identified two previously undocumented mutations in the GAA gene.

Findings:

• Two novel mutations, c.2045A>G (p.Q682R) and c.763C>T (p.Q255X), were discovered in the GAA gene of parents from the studied families.
• These mutations are associated with the genetic basis of Pompe disease in these individuals.
• The identification of novel mutations contributes to the understanding of the genotypic spectrum of Pompe disease.

Implications:

• The discovery of these novel mutations expands the known mutational landscape of Pompe disease.
• This finding aids in genetic counseling and diagnostic efforts for families affected by Pompe disease.
• Further research into the functional impact of these mutations can enhance therapeutic strategies for Pompe disease.