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bioRxiv · 10.1101/2025.08.23.671372

Muscle transcriptome profiling reveals novel molecular pathways and biomarkers in laminin-α2 deficient patients

Pini, V.·Catapano, F.·Bonaccorso, R.·Weisburd, B.·Previtali, S. C.·Muntoni, F.
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Abstract

Merosin-deficient congenital muscular dystrophy (LAMA2-RD) is caused by LAMA2 gene mutations, coding for laminin-211 (merosin) 2 subunit. LAMA2 mutations leading to complete laminin-211 absence result in an invariably severe clinical phenotype, with profound muscle weakness and respiratory insufficiency. Milder phenotypes are often associated with mutations allowing the production of a partially functional protein. While several dysregulated genes/pathways linked to LAMA2-RD muscle loss are known, an in-depth characterization of LAMA2-RD muscle gene expression profile in patients with mutations differentially affecting LAMA2 expression is lacking. We generated muscle transcriptomic data from patients with either complete or partial laminin-211 deficiency, and identified pathways linked to the most dysregulated processes. Genes related to fibrosis, inflammation and metabolism were similarly expressed in both patient cohorts. However, a subset of novel pro-fibrotic and pro-inflammatory genes were exclusively expressed in patients (and mice) completely lacking laminin-211, indicating aspects exacerbated in this cohort. Our work characterizes the main contributors of human LAMA2-RD pathology, providing insight into molecular pathways that could be used as disease biomarkers or as targets for therapeutic approaches.

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Pini, V., Catapano, F., Bonaccorso, R., Weisburd, B., Previtali, S. C., Muntoni, F.. 2025-08-27. Muscle transcriptome profiling reveals novel molecular pathways and biomarkers in laminin-α2 deficient patients. https://doi.org/10.1101/2025.08.23.671372

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