Next generation deep sequencing corrects diagnostic pitfalls of traditional molecular approach in a patient with prenatal onset of Pompe disease

Anne Tsai, Yu Wen Hung, Cary Harding, David Koeller, Jing Wang, Lee Jun C. Wong

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Pompe disease is a rare inherited metabolic disorder of glycogen metabolism caused by mutations in the GAA gene, encoding the acid α-1,4 glucosidase. Successful diagnosis of Pompe disease is achieved by clinical and biochemical evaluation followed by confirmation with DNA testing. Here, we report a male infant with a prenatal onset of cardiac symptoms and enzyme testing consistent with Pompe disease, but DNA testing by Sanger sequencing revealed no pathogenic variants. Due to the strong indication from clinical, enzymatic, and histological studies (despite the absence of molecular confirmation by traditional Sanger sequencing), enzyme replacement therapy (ERT) for Pompe disease was initiated. Reanalysis of the patient's DNA sample using next generation sequencing (NGS) of a panel of target genes causing glycogen storage disorders demonstrated compound heterozygosity for a point mutation and an exonic deletion in the GAA gene. This case illustrates the value of astute clinical judgement in patient management as well as the power of target capture deep NGS in the simultaneous detection of both a point mutation and a heterozygous exonic deletion by correcting pitfalls of the traditional PCR based sequencing, namely; allele dropout and the inability to detect exonic deletions.

Original languageEnglish (US)
Pages (from-to)2500-2504
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume173
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Glycogen Storage Disease Type II
High-Throughput Nucleotide Sequencing
Glycogen
Point Mutation
DNA
Glucosidases
Genes
Enzyme Replacement Therapy
Alleles
Polymerase Chain Reaction
Mutation
Acids
Enzymes

Keywords

  • allele drop-out
  • next generation deep sequencing
  • partial exonic deletion
  • Pompe disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Next generation deep sequencing corrects diagnostic pitfalls of traditional molecular approach in a patient with prenatal onset of Pompe disease. / Tsai, Anne; Hung, Yu Wen; Harding, Cary; Koeller, David; Wang, Jing; Wong, Lee Jun C.

In: American Journal of Medical Genetics, Part A, Vol. 173, No. 9, 01.09.2017, p. 2500-2504.

Research output: Contribution to journalArticle

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