Krit1错义突变导致脑海绵状血管畸形中的剪接错误。
Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation.
作者信息
Verlaan Dominique J, Siegel Adrian M, Rouleau Guy A
机构信息
Center for Research in Neurosciences, Montreal General Hospital, McGill University, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada.
出版信息
Am J Hum Genet. 2002 Jun;70(6):1564-7. doi: 10.1086/340604. Epub 2002 Apr 8.
Abstract
At least 40% of families affected with cerebral cavernous malformation have a mutation in Krit1. We previously identified two point mutations in Krit1 leading to changes in amino acids (D137G and Q210E) in two different families. Further RNA analysis reveals that both point mutations actually activate cryptic splice-donor sites, causing aberrant splicing and leading to a frameshift and protein truncation. To date, no simple missense mutations have been detected in Krit1.
摘要
至少40%患有脑海绵状血管畸形的家族中，Krit1基因存在突变。我们之前在两个不同家族中鉴定出Krit1基因的两个点突变，这些突变导致氨基酸发生变化（D137G和Q210E）。进一步的RNA分析表明，这两个点突变实际上激活了隐匿性剪接供体位点，导致异常剪接，进而引起移码突变和蛋白质截短。迄今为止，尚未在Krit1基因中检测到简单的错义突变。
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本文引用的文献
1
Online Mendelian Inheritance in Man 'OMIM'.《人类孟德尔遗传在线》（OMIM）。
Indian J Dermatol Venereol Leprol. 2003 Nov-Dec;69(6):423-4.
2
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Neurology. 2002 Mar 26;58(6):853-7. doi: 10.1212/wnl.58.6.853.
3
Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation.Krit1与Icap1α之间的相互作用表明，在脑海绵状血管畸形的发病机制中，整合素β1介导的血管生成受到了干扰。
Hum Mol Genet. 2001 Dec 1;10(25):2953-60. doi: 10.1093/hmg/10.25.2953.
4
Identification of eight novel 5'-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1.在编码KRIT1的脑毛细血管畸形基因1（CCM1）中鉴定出八个新的5'-外显子。
Biochim Biophys Acta. 2001 Feb 16;1517(3):464-7. doi: 10.1016/s0167-4781(00)00303-1.
5
CCM1 gene mutations in families segregating cerebral cavernous malformations.患有脑海绵状血管畸形的家族中的CCM1基因突变。
Neurology. 2001 Feb 27;56(4):540-3. doi: 10.1212/wnl.56.4.540.
6
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7
Cloning of the murine Krit1 cDNA reveals novel mammalian 5' coding exons.小鼠Krit1 cDNA的克隆揭示了新的哺乳动物5'编码外显子。
Genomics. 2000 Dec 15;70(3):392-5. doi: 10.1006/geno.2000.6410.
8
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Hum Mol Genet. 1999 Nov;8(12):2325-33. doi: 10.1093/hmg/8.12.2325.
9
Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas.编码KRIT1的CCM1基因的截短突变会导致遗传性海绵状血管瘤。
Nat Genet. 1999 Oct;23(2):189-93. doi: 10.1038/13815.
10
Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27.多位点连锁分析确定了孟德尔式中风（脑海绵状血管畸形）的两个新基因座，分别位于7p15 - 13和3q25.2 - 27。
Hum Mol Genet. 1998 Nov;7(12):1851-8. doi: 10.1093/hmg/7.12.1851.
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