- For the first time, variants in the LEMD2 gene are linked to a muscular dystrophy resembling Emery-Dreifuss muscular dystrophy (EDMD), expanding the known clinical spectrum of LEMD2-related diseases.

 

- The study, published in Brain Pathology, was led by CNAG, the University of Duisburg-Essen (Germany), and the CHEO Research Institute (Canada). 

 

 

 

April 15, 2026. In rare diseases, every new diagnosis is a glimmer of hope for patients, as understanding their condition opens the door to possible treatments, a better quality of life, or a more informed decision within their families. When there is a diagnosis, it takes on average four to five years, in many cases after intensive research and even international collaboration. This is the case of the patient described in a recent study published in the journal Brain Pathology, led by the Centro Nacional de Análisis Genómico (CNAG), the University of Duisburg-Essen (Germany), and the Children’s Hospital of Eastern Ontario Research Institute (Canada).

 

 

Since around 80% of rare disease conditions are genetic, the first steps to identify the underlying cause of a condition include analysing the genome, for example through whole exome sequencing, a technique that focuses on sequencing all protein coding regions of the genome. For this thirteen year old patient, this first step failed to provide a definitive genetic cause. For this reason, researchers went a step further with proteomics on the muscle, a technique that studies and quantifies the full set of proteins expressed, as the patient presented with progressive muscle weakness. This analysis pointed to a new clue for investigation: a significant decrease in LEMD2 protein abundance, in comparison with a cohort of healthy individuals and other neuromuscular disease patients.

 

 

Guided by these findings, a re-analysis of the exome was performed, uncovering two previously unreported, likely pathogenic variants in the LEMD2 gene that explained the underlying cause of the patient’s condition: an Emery–Dreifuss muscular dystrophy (EDMD) like muscle phenotype without cardiomyopathy. The results were further supported by computational analyses indicating that the variants affect a functionally important and conserved region of the LEMD2 protein, as well as by microscopic studies revealing disruptions in the normal organisation of proteins that help maintain the cell nucleus. Beyond reaching a genetic diagnosis for this patient, the study establishes a novel association between LEMD2 and muscular dystrophy, expanding the phenotypic spectrum of this nuclear envelope gene.

 

 

 

LEMD2 is known to play an important role in maintaining the structure of the cell nucleus, organising chromatin and facilitating nuclear envelope re-assembly after cell division. Historically, variants in the LEMD2 gene have been linked mainly to different conditions: juvenile onset cataract with or without arrhythmic cardiomyopathy and Marbach–Rustad progeroid syndrome. Although mild muscle weakness has been reported in some patients, no clear association with severe muscle disease had been described until now. This study adds a new dimension to our understanding of LEMD2 function, expanding the range of clinical features linked to recessive variants in this gene and revealing its involvement in muscle disease, while also highlighting the value of proteomic approaches in uncovering disease related mechanisms.

 

 

The study received funding from the European Union’s Horizon 2020 research and innovation programme through the Marie Skłodowska-Curie grant agreement No. 956148.

 

 

 

REFERENCE ARTICLE

 

Pauper, Marc, et al. ‘A Muscular Dystrophy Associated with Bi‐allelic LEMD2 Variants: Expanding the Genotype of Nuclear Envelopathies’. Brain Pathology, Mar. 2026, p. e70082. DOI.org (Crossref), https://doi.org/10.1111/bpa.70082.