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Collagen VI-related myopathies: clinical variability, phenotype-genotype correlation and exploratory transcriptome
Anna Ky Kwong1, Yanmin Zhang2, Ronnie Sl Ho3
1Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Neuromuscular Disorders : NMD
|April 6, 2023
Summary
This study identified fifteen genetic variants in collagen VI genes (COL6A1, COL6A2, COL6A3) in Chinese patients with Collagen VI-related myopathies. Findings explain varying disease severity and suggest impacts on muscle and skeletal development.
Area of Science:
- Genetics
- Molecular Biology
- Neurology
Background:
- Collagen VI-related myopathies cause muscle weakness and joint contractures.
- Disease severity varies significantly among patients.
- Understanding genetic causes is crucial for diagnosis and treatment.
Purpose of the Study:
- To characterize the clinical and genetic features of 13 Chinese patients with Collagen VI-related myopathies.
- To investigate the impact of identified genetic variants on disease phenotype.
- To explore the molecular mechanisms underlying disease variability.
Main Methods:
- Clinical evaluation of 13 Chinese patients.
- Genetic analysis identifying variants in COL6A1, COL6A2, and COL6A3 genes.
- Histological, radiological, and muscle transcriptomic evaluations.
Main Results:
- Fifteen putative disease-causing variants were identified in COL6A1 (6), COL6A2 (5), and COL6A3 (4).
- Most variants (80%) were dominant-negative, located in the triple helical domain.
- Two novel variants (COL6A1:c.1084_1092del and COL6A2:c.811G>C) were reported.
- Transcriptome data supported extracellular matrix dysfunction and suggested impacts on muscle and skeletal development.
Conclusions:
- Genetic variants in collagen VI genes explain many phenotypes in Collagen VI-related myopathies.
- Dominant-negative variants in the triple helical domain are common.
- Disease severity variability exists and requires further investigation.
- This study provides insights into ethnically Chinese patients with Collagen VI myopathies.
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