Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3
Mutations in apoptosis-related gene, PDCD10, cause cerebral cavernous malformation 3
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DOI：
10.1227/01.neu.0000180811.56157.e1
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发表时间：
2005-11-01
期刊：
影响因子：
4.8
通讯作者：
Gunel, M
中科院分区：
文献类型：
--
作者：
Guclu, B;Ozturk, AK;Gunel, M
目的：在61个有脑海绵状血管畸形（CCM）阳性家族史的家系中，确定CCM3基因，其中8个与CCM3基因座有连锁关系。方法：我们使用高通量筛选技术，温度梯度毛细管电泳，在CCM3间隔内寻找突变。通过该装置检测到的突变随后测序，结果进行了分析。结果：最近的一项研究由Bergametti等。建立程序性细胞死亡10（PDCD10）的基因负责CCM 3。我们在此通过报告61个CCM家族中的4个新突变确认PDCD10为CCM 3基因。这些突变中有两个是相同的，并在外显子7中产生终止密码子。另外两个导致外显子6的移码突变，尽管突变发生在外显子沿着的不同点。最后一个突变导致了外显子9的移码。值得注意的是，这些家族中的突变完全与性状共分离。五个家庭中有三个先前的连锁数据提示的CCM3位点，而剩下的两个被确定在指数患者具有积极的家族史，但没有连锁data.CONCLUSION：我们的数据建立PDCD10的基因负责CCM在家庭中连接到CCM3位点。在KRIT 1和Malcavrnin之后，发现了与CCM遗传形式有关的第三个基因，这是解剖这种疾病的分子病理生理学的重要一步。
OBJECTIVE: To identify the CCM3 gene in a population of 61 families with a positive family history of cerebral cavernous malformations (CCM), 8 of which had suggestive linkage to the CCM3 locus.METHODS: We searched for mutations within the CCM3 interval using a high-throughput screening technique, temperature-gradient capillary electrophoresis. Mutations detected by this device were subsequently sequenced, and the results were analyzed.RESULTS: A recent study by Bergametti et al. established Programmed Cell Death 10 (PDCD10) as the gene responsible for CCM3. We hereby confirm PDCD10 as the CCM3 gene by reporting four novel mutations in 61 CCM families. Two of these mutations were identical and produced a stop codon in exon 7. Another two resulted in frameshift mutations in exon 6, although the mutations occurred at different points along the exon. The last mutation caused a frameshift in exon 9. Of note, mutations in these families completely cosegregated with the trait. Three of the five families had prior linkage data suggestive of the CCM3 locus, whereas the remaining two were identified in index patients with a positive family history but no linkage data.CONCLUSION: Our data establish PDCD10 as the gene responsible for CCM in families linking to the CCM3 locus. The discovery of the third gene involved in inherited forms of CCM, after KRIT1 and Malcavrnin, is an important step toward dissecting the molecular pathophysiology of this disease.