Muscle & nerve · 2025
Tissue-Selective Effects of PLEC Isoform Deficiency: Insights From A Muscle Only Phenotype.
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Gundesli Hulya, Topaloglu Haluk, Dincer Pervin
Аннотация
INTRODUCTION/AIMS: 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.
METHODS: 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.
RESULTS: 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.
DISCUSSION: 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.
METHODS: 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.
RESULTS: 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.
DISCUSSION: 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.