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LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models.

ABSTRACT: Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the LAMA2 gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy affecting patient motor function and reducing life expectancy. However, LAMA2-RD also comprises a developmentally-associated dysmyelinating neuropathy that contributes to the disease progression, in addition to brain abnormalities; the latter often underappreciated. In this brief review, we present data supporting the impact of peripheral neuropathy in the LAMA2-RD phenotype, including both mouse models and human studies. We discuss the molecular mechanisms underlying nerve abnormalities and involved in the laminin-211 pathway, which affects axon sorting, ensheathing and myelination. We conclude with some final considerations of consequences on nerve regeneration and potential therapeutic strategies.

SUBMITTER: Previtali SC

PROVIDER: S-EPMC7190814 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models.

Previtali Stefano Carlo SC Zambon Alberto Andrea AA

Frontiers in molecular neuroscience 20200423

Merosin deficient Congenital Muscular Dystrophy (MDC1A), or LAMA2-related muscular dystrophy (LAMA2-RD), is a recessive disorder resulting from mutations in the <i>LAMA2</i> gene, encoding for the alpha-2 chain of laminin-211. The disease is predominantly characterized by progressive muscular dystrophy affecting patient motor function and reducing life expectancy. However, LAMA2-RD also comprises a developmentally-associated dysmyelinating neuropathy that contributes to the disease progression, ...[more]

PMID: 32390798

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Dataset Information

LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models.

Publications

LAMA2 Neuropathies: Human Findings and Pathomechanisms From Mouse Models.

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