Genetic aspects of the vascular type of Ehlers-Danlos syndrome (vEDS, EDSIV) in Japan
Genetic aspects of the vascular type of Ehlers-Danlos syndrome (vEDS, EDSIV) in Japan
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DOI：
10.1253/circj.71.261
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发表时间：
2007-02-01
影响因子：
3.3
通讯作者：
Shimada, Takashi
中科院分区：
文献类型：
--
作者：
Watanabe, Atsushi;Kosho, Tomoki;Shimada, Takashi
血管型Ehlers-Danlos综合征（vEDS，EDS IV型; MIM#130050）是一种常染色体显性遗传疾病，由III型前胶原（COL 3A 1）基因突变引起。受影响的个人与vEDS是在动脉破裂，动脉瘤，和/或夹层的风险;胃肠道穿孔或破裂;和子宫破裂在怀孕期间，这可能会导致猝死。方法和结果三个无关的日本人表现出症状的vEDS进行了分析。为了鉴定患者RNA中的突变，从培养的皮肤成纤维细胞中制备含有COL 3A 1三螺旋结构域的3.8-kb逆转录酶聚合酶链反应产物，然后直接测序。鉴定了三个杂合突变;具体地说，在三螺旋结构域的（Gly-X-Y）n重复中的2个新的错义碱基取代（Gly 220 Trp，Gly 448 Glu）和COL 3A 1的内含子20的已知剪接供体突变（G+1，IVS 20）。结论日本vEDS患者并发症的类型与相关的COL 3A 1基因突变无关，在COL 3A 1基因诊断后，建立包括临床遗传学家在内的医学专家网络进行遗传咨询，vEDS的长期随访系统可能有助于改善血管和内脏并发症的管理。
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.