COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy
COL3A1 haploinsufficiency results in a variety of Ehlers-Danlos syndrome type IV with delayed onset of complications and longer life expectancy
复制标题
DOI：
10.1097/gim.0b013e3182180c89
复制
发表时间：
2011-08-01
影响因子：
8.8
通讯作者：
Byers, Peter H.
中科院分区：
文献类型：
--
作者：
Leistritz, Dru F.;Pepin, Melanie G.;Byers, Peter H.
目的：探讨血管型ehers - danlos综合征IV型COL3A1突变杂合性的临床结局。方法：我们在19个家族中发现了产生过早终止密码子并导致无义介导的信使RNA衰变的突变。我们回顾了54名COL3A1零突变家庭个体的临床、家族史和医疗并发症。结果：与错义或外显子跳跃突变的个体相比，我们发现寿命延长，首次并发症的年龄延迟了近15年，主要并发症仅限于血管事件。这些家族是在单个个体出现并发症后确定的，但只有28%的亲属，其中一些人已经七八十岁了，没有发生并发症，只有30%的人有Ehlers-Danlos综合征IV型的轻微临床特征。结论：与错意突变和剪接突变相比，零突变的外显率降低，表型似乎几乎完全局限于血管事件。中华医学杂志，2011,13(8):717-722。
Purpose: To characterize the clinical outcome of heterozygosity for COL3A1 null mutations in Ehlers-Danlos syndrome type IV, the vascular type. Methods: We identified mutations that produced premature termination codons and resulted in nonsense-mediated messenger RNA decay in 19 families. We reviewed the clinical and family histories and medical complications in 54 individuals from these families with COL3A1 null mutations. Results: Compared with individuals with missense or exon-skipping mutations, we found that life span was extended, the age of first complication was delayed by almost 15 years, and major complications were limited to vascular events. The families were ascertained after a complication in a single individual, but only 28% of relatives, some of whom had reached their seventies or eighties without incidents, had a complication and only 30% had minor clinical features of Ehlers-Danlos syndrome type IV Conclusion: Null mutations have reduced penetrance compared with missense and splicing mutations, and the phenotype seems to be limited almost entirely to vascular events. Genet Med 2011: 13(8): 717-722.