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Lamar KM, McNally EM. Genetic Modifiers for Neuromuscular Diseases. J Neuromuscul Dis. 2014;1(1):3-13doi: 10.3233/JND-140023.
Lamar, K. M., & McNally, E. M. (2014). Genetic Modifiers for Neuromuscular Diseases. Journal of neuromuscular diseases, 1(1), 3-13. https://doi.org/10.3233/JND-140023
Lamar, Kay-Marie, and McNally, Elizabeth M. "Genetic Modifiers for Neuromuscular Diseases." Journal of neuromuscular diseases vol. 1,1 (2014): 3-13. doi: https://doi.org/10.3233/JND-140023
Lamar KM, McNally EM. Genetic Modifiers for Neuromuscular Diseases. J Neuromuscul Dis. 2014;1(1):3-13. doi: 10.3233/JND-140023. PMID: 25729645; PMCID: PMC4339951.
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J Neuromuscul Dis. 2014;1(1):3-13. doi: 10.3233/JND-140023.

Genetic Modifiers for Neuromuscular Diseases.

Journal of neuromuscular diseases

Kay-Marie Lamar, Elizabeth M McNally

Affiliations

  1. Department of Human Genetics, Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL, USA.

PMID: 25729645 PMCID: PMC4339951 DOI: 10.3233/JND-140023

Abstract

Neuromuscular diseases, which encompass disorders that affect muscle and its innervation, are highly heritable. Genetic diagnosis now frequently pinpoints the primary mutation responsible for a given neuromuscular disease. However, the results from genetic testing indicate that neuromuscular disease phenotypes may vary widely, even in individuals with the same primary disease-causing mutation. Clinical variability arises from both genetic and environmental factors. Genetic modifiers can now be identified using candidate gene as well as genomic approaches. The presence of genetic modifiers for neuromuscular disease helps define the clinical outcome and also highlights pathways of potential therapeutic utility. Herein, we will focus on single gene neuromuscular disorders, including muscular dystrophy, spinal muscular atrophy, and amyotrophic lateral sclerosis, and the methods that have been used to identify modifier genes. Animal models have been an invaluable resource for modifier gene discovery and subsequent mechanistic studies. Some modifiers, identified using animal models, have successfully translated to the human counterpart. Furthermore, in a few instances, modifier gene discovery has repetitively uncovered the same pathway, such as TGFβ signaling in muscular dystrophy, further emphasizing the relevance of that pathway. Knowledge of genetic factors that influence disease can have direct clinical applications for prognosis and predicted outcome.

Keywords: Genetic modifier; amyotrophic lateral sclerosis; muscular dystrophy; spinal muscular atrophy

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