Altered Splicing of LAMP2 in a Multigenerational Family from Latvia Affected by Danon Disease
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Date
2024-01
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Abstract
Background and Objectives: Danon disease is a multisystemic disorder associated with variants in the LAMP2 gene, mainly affecting the cardiac muscle. Here, we report a multigenerational family from Latvia with two male patients, hemizygous for a novel splice-affecting variant c.928+3A>G. Affected patients exhibit a cardiac phenotype, moderate mental disability, and mild retinal changes. Materials and Methods: Both patients underwent either exome or hypertrophic cardiomyopathy gene panel next-generation sequencing. The pathogenic variant effect was determined using reverse transcription, Sanger sequencing, and high-resolution electrophoresis. Results: Evaluation of the splicing process revealed that approximately 80% of the transcripts exhibited a lack of the entire exon 7. This alteration was predicted to cause a shift of the reading frame, consequently introducing a premature stop codon downstream in the sequence. Conclusions: Based on our data, we propose that c.928+3A>G is a pathogenic variant associated with Danon disease.
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Publisher Copyright: © 2024 by the authors.
Keywords
altered splicing, Danon disease, LAMP2, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, General Medicine
Citation
Stavusis, J, Mičule, I, Grīnfelde, I, Zdanovica, A, Pudulis, J, Valeina, S, Sepetiene, S, Lace, B & Inashkina, I 2024, 'Altered Splicing of LAMP2 in a Multigenerational Family from Latvia Affected by Danon Disease', Medicina (Lithuania), vol. 60, no. 1, 99. https://doi.org/10.3390/medicina60010099