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COL1‐related overlap disorder : a novel connective tissue disorder incorporating the osteogenesis imperfecta/Ehlers‐Danlos syndrome overlap

Author
Organization
Abstract
The 2017 classification of Ehlers-Danlos syndromes (EDS) identifies three types associated with causative variants in COL1A1/COL1A2 and distinct from osteogenesis imperfecta (OI). Previously, patients have been described with variable features of both disorders, and causative variants in COL1A1/COL1A2; but this phenotype has not been included in the current classification. Here, we expand and re-define this OI/EDS overlap as a missing EDS type. Twenty-one individuals from 13 families were reported, in whom COL1A1/COL1A2 variants were found after a suspicion of EDS. None of them could be classified as affected by OI or by any of the three recognized EDS variants associated with COL1A1/COL1A2. This phenotype is dominated by EDS-related features. OI-related features were limited to mildly reduced bone mass, occasional fractures and short stature. Eight COL1A1/COL1A2 variants were novel and five recurrent with a predominance of glycine substitutions affecting residues within the procollagen N-proteinase cleavage site of alpha 1(I) and alpha 2(I) procollagens. Selected variants were investigated by biochemical, ultrastructural and immunofluorescence studies. The pattern of observed changes in the dermis and in vitro for selected variants was more typical of EDS rather than OI. Our findings indicate the existence of a wider recognizable spectrum associated with COL1A1/COL1A2.
Keywords
Ehlers-Danlos syndrome, joint hypermobility, osteogenesis imperfecta, HETEROZYGOUS MUTATION, CYSTEINE SUBSTITUTION, JOINT HYPERMOBILITY, I COLLAGEN, COL1A1, CHAIN, INTEGRIN, PHENOTYPE, DIAGNOSIS, FAMILY

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MLA
Morlino, Silvia, et al. “COL1‐related Overlap Disorder : A Novel Connective Tissue Disorder Incorporating the Osteogenesis Imperfecta/Ehlers‐Danlos Syndrome Overlap.” CLINICAL GENETICS, 2020.
APA
Morlino, S., Micale, L., Ritelli, M., Rohrbach, M., Zoppi, N., Vandersteen, A., … Castori, M. (2020). COL1‐related overlap disorder : a novel connective tissue disorder incorporating the osteogenesis imperfecta/Ehlers‐Danlos syndrome overlap. CLINICAL GENETICS.
Chicago author-date
Morlino, Silvia, Lucia Micale, Marco Ritelli, Marianne Rohrbach, Nicoletta Zoppi, Anthony Vandersteen, Sara Mackay, et al. 2020. “COL1‐related Overlap Disorder : A Novel Connective Tissue Disorder Incorporating the Osteogenesis Imperfecta/Ehlers‐Danlos Syndrome Overlap.” CLINICAL GENETICS.
Chicago author-date (all authors)
Morlino, Silvia, Lucia Micale, Marco Ritelli, Marianne Rohrbach, Nicoletta Zoppi, Anthony Vandersteen, Sara Mackay, Emanuele Agolini, Dario Cocciadiferro, Erina Sasaki, Annalisa Madeo, Alessandro Ferraris, Willie Reardon, Maja Di Rocco, Antonio Novelli, Paola Grammatico, Fransiska Malfait, Tommaso Mazza, Alan Hakim, Cecilia Giunta, Marina Colombi, and Marco Castori. 2020. “COL1‐related Overlap Disorder : A Novel Connective Tissue Disorder Incorporating the Osteogenesis Imperfecta/Ehlers‐Danlos Syndrome Overlap.” CLINICAL GENETICS.
Vancouver
1.
Morlino S, Micale L, Ritelli M, Rohrbach M, Zoppi N, Vandersteen A, et al. COL1‐related overlap disorder : a novel connective tissue disorder incorporating the osteogenesis imperfecta/Ehlers‐Danlos syndrome overlap. CLINICAL GENETICS. 2020;
IEEE
[1]
S. Morlino et al., “COL1‐related overlap disorder : a novel connective tissue disorder incorporating the osteogenesis imperfecta/Ehlers‐Danlos syndrome overlap,” CLINICAL GENETICS, 2020.
@article{8638763,
  abstract     = {The 2017 classification of Ehlers-Danlos syndromes (EDS) identifies three types associated with causative variants in COL1A1/COL1A2 and distinct from osteogenesis imperfecta (OI). Previously, patients have been described with variable features of both disorders, and causative variants in COL1A1/COL1A2; but this phenotype has not been included in the current classification. Here, we expand and re-define this OI/EDS overlap as a missing EDS type. Twenty-one individuals from 13 families were reported, in whom COL1A1/COL1A2 variants were found after a suspicion of EDS. None of them could be classified as affected by OI or by any of the three recognized EDS variants associated with COL1A1/COL1A2. This phenotype is dominated by EDS-related features. OI-related features were limited to mildly reduced bone mass, occasional fractures and short stature. Eight COL1A1/COL1A2 variants were novel and five recurrent with a predominance of glycine substitutions affecting residues within the procollagen N-proteinase cleavage site of alpha 1(I) and alpha 2(I) procollagens. Selected variants were investigated by biochemical, ultrastructural and immunofluorescence studies. The pattern of observed changes in the dermis and in vitro for selected variants was more typical of EDS rather than OI. Our findings indicate the existence of a wider recognizable spectrum associated with COL1A1/COL1A2.},
  author       = {Morlino, Silvia and Micale, Lucia and Ritelli, Marco and Rohrbach, Marianne and Zoppi, Nicoletta and Vandersteen, Anthony and Mackay, Sara and Agolini, Emanuele and Cocciadiferro, Dario and Sasaki, Erina and Madeo, Annalisa and Ferraris, Alessandro and Reardon, Willie and Di Rocco, Maja and Novelli, Antonio and Grammatico, Paola and Malfait, Fransiska and Mazza, Tommaso and Hakim, Alan and Giunta, Cecilia and Colombi, Marina and Castori, Marco},
  issn         = {0009-9163},
  journal      = {CLINICAL GENETICS},
  keywords     = {Ehlers-Danlos syndrome,joint hypermobility,osteogenesis imperfecta,HETEROZYGOUS MUTATION,CYSTEINE SUBSTITUTION,JOINT HYPERMOBILITY,I COLLAGEN,COL1A1,CHAIN,INTEGRIN,PHENOTYPE,DIAGNOSIS,FAMILY},
  language     = {eng},
  title        = {COL1‐related overlap disorder : a novel connective tissue disorder incorporating the osteogenesis imperfecta/Ehlers‐Danlos syndrome overlap},
  url          = {http://dx.doi.org/10.1111/cge.13683},
  year         = {2020},
}

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