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Cited by 111Muscle Physiology and DisordersConnective tissue disorders researchGenomics and Rare Diseases

Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy

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Hicks, D., Farsani, G. T., Laval, S., Collins, J., Sarkozy, A., Martoni, E., Shah, A., Zou, Y. +6 more·2014·Human Molecular Genetics
DOI 10.1093/hmg/ddt637
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Abstract

Bethlem myopathy (BM) [MIM 158810] is a slowly progressive muscle disease characterized by contractures and proximal weakness, which can be caused by mutations in one of the collagen VI genes (COL6A1, COL6A2 and COL6A3). However, there may be additional causal genes to identify as in ∼50% of BM cases no mutations in the COL6 genes are identified. In a cohort of -24 patients with a BM-like phenotype, we first sequenced 12 candidate genes based on their function, including genes for known binding partners of collagen VI, and those enzymes involved in its correct post-translational modification, assembly and secretion. Proceeding to whole-exome sequencing (WES), we identified mutations in the COL12A1 gene, a member of the FACIT collagens (fibril-associated collagens with interrupted triple helices) in five individuals from two families. Both families showed dominant inheritance with a clinical phenotype resembling classical BM. Family 1 had a single-base substitution that led to the replacement of one glycine residue in the triple-helical domain, breaking the Gly-X-Y repeating pattern, and Family 2 had a missense mutation, which created a mutant protein with an unpaired cysteine residue. Abnormality at the protein level was confirmed in both families by the intracellular retention of collagen XII in patient dermal fibroblasts. The mutation in Family 2 leads to the up-regulation of genes associated with the unfolded protein response (UPR) pathway and swollen, dysmorphic rough-ER.…

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Crossref · 10.1093/hmg/ddt637

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  • The patients reported by Hicks et al. [2014] (n=5) developed long finger flexions (n=4), rigid spine (n=2), flexion contractures of knee (n=2), elbow (n=1), and wrist (n=1).

    “The patients reported by Hicks et al. [2014] (n ¼ 5) developed long finger flexions (n ¼ 4), rigid spine (n ¼ 2), flexion contractures of knee (n ¼ 2), elbow (n ¼ 1), and wrist (n ¼ 1).”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Hicks et al., 2014

  • Through these studies they identified eight patients in four families that presented with autosomal recessive (two patients, one family) and dominant (six patients, three families) forms of EDS/myopathy.

    “Through these studies they identified eight patients in four families that presented with autosomal recessive (two patients, one family) and dominant (six patients, three families) forms of EDS/myopathy.”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Hicks et al., 2014

  • Their age at publication ranged from birth to 48 years.

    “Their age at publication ranged from birth to 48 years (Table S1) [Hicks et al., 2014;Zou et al., 2014;Punetha et al., 2016].”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Hicks et al., 2014

  • Zou et al. [2014] and Hicks et al. [2014] investigated groups of patients that had some symptoms of these myopathies but presented with a distinctive phenotype and did not have mutations affecting type VI collagen.

    “Zou et al. [2014] andHicks et al. [2014] investigated groups of patients that had some symptoms of these myopathies but presented with a distinctive phenotype and did not have mutations affecting type VI collagen.”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Hicks et al., 2014

  • To date, nine patients from five families with myopathic EDS have been reported.

    “To date, nine patients from five families with myopathic EDS have been reported [Hicks et al., 2014;Zou et al., 2014;Punetha et al., 2016]”

    From The Ehlers–Danlos syndromes, rare types (2017) · cites this paper as Hicks et al., 2014

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Authors
Hicks, D., Farsani, G. T., Laval, S., Collins, J., Sarkozy, A., Martoni, E., Shah, A., Zou, Y., Koch, M., Bonnemann, C. G., Roberts, M., Lochmuller, H., Bushby, K., & Straub, V.
Affiliations
  • Cincinnati Children's Hospital Medical Center (US)
  • University of Ferrara (IT)
  • National Institutes of Health (US)
  • University of Cologne (DE)
  • Salford Royal Hospital (GB)
Corresponding author
Straub, V.
ORCID
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2013-12-13
Volume
23
Issue
9
Pages
2353-2363
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/ddt637
OpenAlex
W2113936735
Cited by
111
References
2
Citations by year
2026: 2 · 2025: 10 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 12 · 2020: 15 · 2019: 8 · 2018: 6 · 2017: 3 · 2016: 10 · 2015: 7 · 2014: 5 · 2013: 1
FWCI
3.44
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • National Institute for Health and Care Research (NF-SI-0512-10036)
  • Newcastle University
  • University of Glasgow
  • Muscular Dystrophy UK
  • Fonds de Recherche du Québec - Santé
  • Medical Research Council (MR/K000608/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
Keywords
Bethlem myopathy, collagen XII, COL12A1, collagen VI, collagen post-translational modification, collagen secretion, intracellular retention, unfolded protein response, rough endoplasmic reticulum, missense mutations, glycine substitution, dominant inheritance
MeSH terms
Adolescent, Adult, Child, Collagen, Extracellular Matrix, Female, Humans, Male, Middle Aged, Muscular Diseases, Mutation, Genetic Predisposition to Disease, Collagen Type XII, Collagen Type VI, Young Adult

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