Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.763240
Keywords
Danon disease; LAMP2; splicing mutation; targeted sequencing; genetic diagnosis
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Danon disease is a rare glycogen storage lysosomal disorder caused by mutations in the LAMP2 gene. A specific family with a novel pathogenic splice-altering mutation in the LAMP2 gene showed cardiac-only symptoms, including frequent ventricular tachycardia, intraventricular block, and hypertrophic cardiomyopathy. Minigene assays revealed that the mutation led to abnormal intron retention, resulting in protein truncation and instability.
Danon disease (DD) is a rare glycogen storage lysosomal disorder caused by mutations in the LAMP2 gene. Patients with DD are usually characterized clinically by severe multisystem syndromes. We describe a specific family with a novel pathogenic splice-altering mutation in the LAMP2 gene (c.741+2T>C) with cardiac-only symptoms (frequent ventricular tachycardia, intraventricular block, and hypertrophic cardiomyopathy). Minigene assays were used to evaluate the consequence of the splice-site mutation in the LAMP2 gene. The results showed that the c.741+2T>C mutation led to extra 6-bp preservation of intron 5 at the junction between exons 5 and 6 during transcriptional processing of the mRNA, which creates a stop codon and truncated the LAMP2 protein to 248-amino-acid residues. The mutant LAMP2 protein was predicted to have a conformational change, lacks the important transmembrane domain, and subsequent protein destabilization.
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