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


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.


CONCLUSIONS
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.
Watanabe
Atsushi
A
Division of Clinical Genetics, Nippon Medical School Main Hospital, Tokyo, Japan. aw3703@nms.ac.jp
Kosho
Tomoki
T
Wada
Takahiro
T
Sakai
Noriyasu
N
Fujimoto
Mitsuo
M
Fukushima
Yoshimitsu
Y
Shimada
Takashi
T
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002478:Cells, Cultured; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree
C439971:COL3A1 protein, human; D024061:Collagen Type III; D004247:DNA