Genetic aspects of the vascular type of Ehlers-Danlos syndrome (vEDS, EDSIV) in Japan

Circ J. 2007 Feb;71(2):261-5. doi: 10.1253/circj.71.261.

Abstract

Background: The vascular type of Ehlers-Danlos syndrome (vEDS, EDS type IV; MIM#130050) is an autosomal dominantly inherited disorder that results from mutations in the genes for type III procollagen (COL3A1). Affected individuals with vEDS are at risk of arterial rupture, aneurysm, and/or dissection; gastrointestinal perforation or rupture; and uterine rupture during pregnancy, which may lead to sudden death.

Methods and results: Three unrelated Japanese individuals who exhibited symptoms of vEDS were analyzed. In order to identify mutations in the patients' RNA, one 3.8-kb reverse transcriptase polymerase chain reaction product containing the triple-helical domain of COL3A1 was prepared from cultured skin fibroblasts and then was sequenced directly. Three heterozygous mutations were identified; specifically, 2 novel missense base substitutions (Gly220Trp, Gly448Glu) in the (Gly-X-Y)n repeat of the triple-helical domain and a known splicing donor mutation of intron 20 (G+1, IVS20) of COL3A1. The genotype-phenotype correlations in Japanese vEDS individuals with COL3A1 mutations were also investigated.

Conclusion: There was no association between the type of complications in vEDS and the related COL3A1 mutation found. After the genetic diagnosis of COL3A1, the establishment of both a network among medical specialists, including clinical geneticists to perform genetic counseling, and long-term follow-up systems of vEDS may help to improve the management of vascular and visceral complications.

MeSH terms

  • Adolescent
  • Adult
  • Asian Continental Ancestry Group / genetics*
  • Cells, Cultured
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • DNA / genetics
  • Ehlers-Danlos Syndrome / diagnosis
  • Ehlers-Danlos Syndrome / genetics*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Japan
  • Male
  • Mutation / genetics*
  • Pedigree

Substances

  • COL3A1 protein, human
  • Collagen Type III
  • DNA