Evidence map›Paper›PMID 39923201›Full record

ArticleAnnals of clinical and translational neurology2025

Clinical characterization of Collagen XII-related disease caused by biallelic COL12A1 variants.

Riley M McCarty, Dimah Saade, Pinki Munot, Chamindra G Laverty, Hailey Pinz, Yaqun Zou, Meghan McAnally, Pomi Yun, Cuixia Tian, Ying Hu and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Myopathic Ehlers-Danlos Syndrome (mEDS) Related toInternational journal of molecular sciences · 2025
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Riley M McCartyNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Dimah SaadeNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Pinki MunotThe Dubowitz Neuromuscular Centre, Great Ormond Street Institute of Child Health, London, UK.
Chamindra G LavertyDepartment of Neurosciences, University of California San Diego, San Diego, California, USA.
Hailey PinzDivision of Medical Genetics, Saint Louis University, St. Louis, Missouri, USA.
Yaqun ZouNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Meghan McAnallyNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Pomi YunNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Cuixia TianDivision of Neurology, Cincinnati Children's Hospital Medical Center & Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio, USA.
Ying HuNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Lucy FengThe Dubowitz Neuromuscular Centre, Great Ormond Street Institute of Child Health, London, UK.
Rahul PhadkeDubowitz Neuromuscular Centre, Division of Neuropathology, UCL Queen Square Institute of Neurology, Queen Square, London, UK.
Sophia CeulemansDivision of Genetics, Rady Children's Hospital, San Diego, California, USA.
Pilar MagoulasDepartment of Genetics, Texas Children's Hospital, Houston, Texas, USA.
Andrew J SkalskyDivision of Pediatric Rehabilitation Medicine, Rady's Children's Hospital, San Diego, California, USA.
Jennifer R FriedmanDepartment of Neurosciences, University of California San Diego, San Diego, California, USA.
Stephen R BraddockDivision of Medical Genetics, Saint Louis University, St. Louis, Missouri, USA.
Sarah B NeuhausNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Denise M MalickiDepartment of Pathology, Rady Children's Hospital, San Diego, California, USA.
Matthew N BainbridgeRady Children's Institute of Genomic Medicine, San Diego, California, USA.
Shareef NahasRady Children's Institute of Genomic Medicine, San Diego, California, USA.
David P DimmockRady Children's Institute of Genomic Medicine, San Diego, California, USA.
Stephen F KingsmoreRady Children's Institute of Genomic Medicine, San Diego, California, USA.
Timothy E LotzeDivision of Neurology and Developmental Neuroscience, Baylor College of Medicine/Texas Children's Hospital, Houston, Texas, USA.
A Reghan FoleyNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0003-2168-1119
Francesco MuntoniThe Dubowitz Neuromuscular Centre, Great Ormond Street Institute of Child Health, London, UK.
Volker StraubJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Sandra DonkervoortNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-6399-1444
Carsten G BönnemannNeuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0002-5930-2324

Funding

Coalition to Cure Calpain 3GenzymeIntramural funds from the NIH National Institute of Neurological Disorders and StrokeLGMD2D Foundation and Kurt+Peter FoundationLGMD2I Research FundMuscular Dystrophy UKNIHNIHR Newcastle Biomedical Research Centre (BRC)NINDS NIH HHSSamantha J. Brazzo FoundationSanofiUltragenyx Pharmaceutical
6 · The paper itself

Abstract

objectiveWhile there have been several reports of patients with dominantly acting COL12A1 variants, few cases of the more severe recessive Collagen XII-related disorders have previously been documented.

methodsWe present detailed clinical, immunocytochemical, and imaging data on eight additional patients from seven families with biallelic pathogenic variants in COL12A1.

resultsAll patients presented with a consistent constellation of congenital onset clinical features: hypotonia, dysmorphic features, most notably gingival hypertrophy, prominent distal joint hyperlaxity, with co-occurring contractures of large joints, and variable muscle involvement, evident both clinically and on muscle imaging. Five patients presented with a severe congenital phenotype manifesting with profound weakness, significantly delayed or minimal attainment of motor milestones, respiratory insufficiency, and feeding difficulties. Three patients presented with mild-to-moderate muscle weakness and delayed milestones but were able to achieve independent ambulation. Patients were found to have biallelic loss-of-function COL12A1 variants, except for one family (p.I1393Ffs*11/p.A1110D). Consistent with the variable clinical spectrum, in vitro immunocytochemistry analysis in fibroblasts ranged from complete absence of Collagen XII expression in a patient with severe disease, to a mild reduction in a patient with milder disease.

interpretationHere we characterize the clinical presentation, muscle imaging, and dermal fibroblast immunostaining findings associated with biallelic variants in COL12A1, further establishing COL12A1 as a recessive myopathic Ehlers-Danlos syndrome (mEDS) gene, and expanding the clinical spectrum to include a milder EDS phenotype.

Indexed as

Collagen Type XIIEhlers-Danlos SyndromeAdolescentAdultChildChild, PreschoolFemaleHumansInfantMalePhenotypeCOL12A1 protein, humanCollagen Type XII

Identifiers

PMID39923201
PMCPMC11920742

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.