Tissue-Selective Effects of PLEC Isoform Deficiency: Insights From A Muscle Only Phenotype

The functional diversity of the PLEC gene is largely attributed to its multiple tissue-specific transcript isoforms. This study investigated the tissue-specific differential expression of plectin transcript isoforms in a patient with plectin 1f deficiency who presented solely with muscular dystrophy (LGMDR17) and lacked epidermolysis bullosa simplex (EBS) symptoms. We aimed to characterize the isoform-specific expression patterns that may underlie this tissue-restricted pathology.

RNA was isolated from skeletal muscle tissue and primary fibroblast cells of both the patient and a healthy control. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression levels of total PLEC and its isoforms. Semi-quantitative PCR was also performed in fibroblasts to evaluate the total PLEC expression.

In the patient's muscle tissue, PLEC 1b and 1d isoforms were downregulated compared to the control. In contrast, a semi-quantitative analysis revealed an increase in total PLEC expression level within primary fibroblasts. Furthermore, RT-qPCR analyses validated the upregulation of mRNA expressions for total PLEC (5.6-fold) and its isoforms PLEC 1, 1a, 1b, and 1d (2.8; 5; 1.4; 4.2-fold, respectively) in these cells. PLEC 1c, 1e, and 1g exhibited either unchanged or undetectable expression in both fibroblast and muscle samples from the patient compared to control.

These findings suggest that tissue-specific regulation of PLEC isoforms may explain the absence of skin involvement in plectin 1f deficiency. Understanding the molecular mechanisms behind isoform-specific expression in a tissue-selective manner could inform novel therapeutic strategies for LGMDR17 and other PLEC-related disorders.