Advanced search
1 file | 616.14 KB

Ehlers-Danlos syndrome, hypermobility type, is linked to chromosome 8p22-8p21.1 in an extended Belgian family

Delfien Syx (UGent) , Sofie Symoens (UGent) , Wouter Steyaert (UGent) , Anne De Paepe (UGent) , Paul Coucke (UGent) and Fransiska Malfait (UGent)
Author
Organization
Abstract
Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDSHT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in the LZTS1 gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition.
Keywords
TUMOR-SUPPRESSOR GENE, JOINT HYPERMOBILITY, MUTATIONS, PRIORITIZATION, IDENTIFICATION, ABNORMALITIES, CANDIDATES, UPDATE, LZTS1

Downloads

  • Syx et al 2015 DM2015-828970.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 616.14 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Syx, Delfien, Sofie Symoens, Wouter Steyaert, Anne De Paepe, Paul Coucke, and Fransiska Malfait. 2015. “Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family.” Disease Markers.
APA
Syx, D., Symoens, S., Steyaert, W., De Paepe, A., Coucke, P., & Malfait, F. (2015). Ehlers-Danlos syndrome, hypermobility type, is linked to chromosome 8p22-8p21.1 in an extended Belgian family. DISEASE MARKERS.
Vancouver
1.
Syx D, Symoens S, Steyaert W, De Paepe A, Coucke P, Malfait F. Ehlers-Danlos syndrome, hypermobility type, is linked to chromosome 8p22-8p21.1 in an extended Belgian family. DISEASE MARKERS. 2015;
MLA
Syx, Delfien et al. “Ehlers-Danlos Syndrome, Hypermobility Type, Is Linked to Chromosome 8p22-8p21.1 in an Extended Belgian Family.” DISEASE MARKERS (2015): n. pag. Print.
@article{8560585,
  abstract     = {Joint hypermobility is a common, mostly benign, finding in the general population. In a subset of individuals, however, it causes a range of clinical problems, mainly affecting the musculoskeletal system. Joint hypermobility often appears as a familial trait and is shared by several heritable connective tissue disorders, including the hypermobility subtype of the Ehlers-Danlos syndrome (EDSHT) or benign joint hypermobility syndrome (BJHS). These hereditary conditions provide unique models for the study of the genetic basis of joint hypermobility. Nevertheless, these studies are largely hampered by the great variability in clinical presentation and the often vague mode of inheritance in many families. Here, we performed a genome-wide linkage scan in a unique three-generation family with an autosomal dominant EDS-HT phenotype and identified a linkage interval on chromosome 8p22-8p21.1, with a maximum two-point LOD score of 4.73. Subsequent whole exome sequencing revealed the presence of a unique missense variant in the LZTS1 gene, located within the candidate region. Subsequent analysis of 230 EDS-HT/BJHS patients resulted in the identification of three additional rare variants. This is the first reported genome-wide linkage analysis in an EDS-HT family, thereby providing an opportunity to identify a new disease gene for this condition.},
  articleno    = {828970},
  author       = {Syx, Delfien and Symoens, Sofie and Steyaert, Wouter and De Paepe, Anne and Coucke, Paul and Malfait, Fransiska},
  issn         = {0278-0240},
  journal      = {DISEASE MARKERS},
  keywords     = {TUMOR-SUPPRESSOR GENE,JOINT HYPERMOBILITY,MUTATIONS,PRIORITIZATION,IDENTIFICATION,ABNORMALITIES,CANDIDATES,UPDATE,LZTS1},
  language     = {eng},
  pages        = {9},
  title        = {Ehlers-Danlos syndrome, hypermobility type, is linked to chromosome 8p22-8p21.1 in an extended Belgian family},
  url          = {http://dx.doi.org/10.1155/2015/828970},
  year         = {2015},
}

Altmetric
View in Altmetric
Web of Science
Times cited: