Glycogen storage disease type II, or Pompe disease, is an autosomal recessive disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA). We performed genetic analysis to confirm the diagnosis of Pompe disease in a 61-year-old patient with progressive weakness in extremities, severe Sleep Apnea-Hypopnea Syndrome, a significant reduction of alpha-glucosidase in liquid sample of peripheral blood and muscular biopsy diagnosis. GAA gene sequencing showed the patient is homozygous for the splice-site mutation c.1194+5G>A, considered as nonpathogenic in Pompe Center mutation database. Further molecular RNA characterization of GAA transcripts allowed us to identify abnormal processing of pre-mRNA, leading to aberrant transcripts and a significant reduction of GAA mRNA levels. Our results indicate that c.1194+5G>A is a pathogenic splice-site mutation and should be considered as such for diagnostic purposes. This study emphasizes the potential role of functional studies to determine the consequences of mutations with no evident pathogenicity.
Keywords: Functional characterization; Pompe disease; Splicing mutation.
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