ArticleAnnals of clinical and translational neurology2019
Dominant collagen XII mutations cause a distal myopathy.
Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Myopathic Ehlers-Danlos Syndrome (mEDS) Related toInternational journal of molecular sciences · 2025Review
- Novel variant of COL12A1 gene causing neonatal hypotonia and respiratory failure.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Collagen type VI regulates TGF-β bioavailability in skeletal muscle in mice.The Journal of clinical investigation · 2025Article
- Clinical characterization of Collagen XII-related disease caused by biallelic COL12A1 variants.Annals of clinical and translational neurology · 2025Article
- Dominantly inherited muscle disorders: understanding their complexity and exploring therapeutic approaches.Disease models & mechanisms · 2024Review
- The shared molecular mechanism of spinal cord injury and sarcopenia: a comprehensive genomics analysis.Frontiers in neurology · 2024Article
- Ablation of collagen XII disturbs joint extracellular matrix organization and causes patellar subluxation.iScience · 2023Article
- Prevalence of Monogenic Bone Disorders in a Dutch Cohort of Atypical Femur Fracture Patients.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Collagen XII regulates stromal wound closure.Experimental eye research · 2023Article
- SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Collagen XII mediated cellular and extracellular mechanisms in development, regeneration, and disease.Frontiers in cell and developmental biology · 2023Review
- Targeted conditional collagen XII deletion alters tendon function.Matrix biology plus · 2022Article
- Article
- Collagen XII Regulates Corneal Stromal Structure by Modulating Transforming Growth Factor-β Activity.The American journal of pathology · 2022Article
- A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita.Genes · 2021Article
- Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis.Nature medicine · 2021Article
- Collagen XII mediated cellular and extracellular mechanisms regulate establishment of tendon structure and function.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- GGPS1 Mutations Cause Muscular Dystrophy/Hearing Loss/Ovarian Insufficiency Syndrome.Annals of neurology · 2020Article
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22 authors.
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Abstract
objectiveTo characterize the natural history and clinical features of myopathies caused by mono-allelic, dominantly acting pathogenic variants in COL12A1.
methodsPatients with dominant COL12A1-related myopathies were characterized by history and clinical examination, muscle imaging, and genetic analysis. Pathogenicity of the variants was assessed by immunostaining patient-derived dermal fibroblast cultures for collagen XII.
resultsFour independent families with childhood-onset weakness due to novel, dominantly acting pathogenic variants in COL12A1 were identified. Adult patients exhibited distal-predominant weakness. Three families carried dominantly acting glycine missense variants, and one family had a heterozygous, intragenic, in-frame deletion of exon 52 of COL12A1. All pathogenic variants resulted in increased intracellular retention of collagen XII in patient-derived fibroblasts as well as loss of extracellular, fibrillar collagen XII deposition. Since haploinsufficiency for COL12A1 is largely clinically asymptomatic, we designed and evaluated small interfering RNAs (siRNAs) that specifically target the mutant allele containing the exon 52 deletion. Immunostaining of the patient fibroblasts treated with the siRNA showed a near complete correction of collagen XII staining patterns.
interpretationThis study characterizes a distal myopathy phenotype in adults with dominant COL12A1 pathogenic variants, further defining the phenotypic spectrum and natural history of COL12A1-related myopathies. This work also provides proof of concept of a precision medicine treatment approach by proposing and validating allele-specific knockdown using siRNAs specifically designed to target a patient's dominant COL12A1 disease allele.
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