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Case Report: A Novel LAMP2 Splice-Altering Mutation Causes Cardiac-Only Danon Disease.

ABSTRACT: 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.

SUBMITTER: Li Z

PROVIDER: S-EPMC8655779 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Case Report: A Novel LAMP2 Splice-Altering Mutation Causes Cardiac-Only Danon Disease.

Li Zongzhe Z Ma Fei F Li Rui R Xiao Zhichao Z Zeng Hesong H Wang Dao Wen DW

Frontiers in cardiovascular medicine 20211125

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 spli ...[more]

PMID: 34901223

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