Cerebral cavernous malformations: From genes to proteins to disease - Clinical article

Journal of Neurosurgery

Volumn 116, Issue 1, 2012, Pages 122-132

  Cavalcanti, Daniel D ^a   Kalani, M Yashar S ^a   Martirosyan, Nikolay L ^a   Eales, Justin ^a   Spetzler, Robert F ^a   Preul, Mark C ^a  

^a BARROW NEUROLOGICAL INSTITUTE   (United States)

Author keywords

CCM1; CCM2; CCM3; Cerebral cavernous malformation; Cerebrovascular disease; Gene; KRIT1; MGC4607; PDCD10; Protein; Stroke; Vascular disorders

Indexed keywords

ICAP1A PROTEIN; KRIT1 PROTEIN; PDCD10 PROTEIN; PROTEIN; RAP1A PROTEIN; SNX17 PROTEIN; UNCLASSIFIED DRUG;

CAVERNOUS HEMANGIOMA; CHROMOSOME 3Q; CHROMOSOME 7P; CLINICAL FEATURE; GENE DELETION; GENE IDENTIFICATION; GENE LOCUS; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; HUMAN; MOLECULAR GENETICS; MOLECULAR INTERACTION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REVIEW;

GENETIC LOCI; HEMANGIOMA, CAVERNOUS, CENTRAL NERVOUS SYSTEM; HUMANS; MUTATION; NEOVASCULARIZATION, PATHOLOGIC; SIGNAL TRANSDUCTION;

EID: 84855404378     PISSN: 00223085     EISSN: 19330693     Source Type: Journal    
DOI: 10.3171/2011.8.JNS101241     Document Type: Review

References (114)

1. Abe M, Kjellberg RN, Adams RD: Clinical presentations of vascular malformations of the brain stem: comparison of angiographically positive and negative types. J Neurol Neurosurg Psychiatry 52:167-175, 1989 (Pubitemid 19054189)
2. Béraud-Dufour S, Gautier R, Albiges-Rizo C, Chardin P, Faurobert E: Krit 1 interactions with microtubules and membranes are regulated by Rap1 and integrin cytoplasmic domain associated protein-1. FEBS J 274:5518-5532, 2007 (Pubitemid 47622064)
3. Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, et al: Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet 76:42-51, 2005 (Pubitemid 40023764)
4. Bicknell JM: Familial cavernous angioma of the brain stem dominantly inherited in Hispanics. Neurosurgery 24:102-105, 1989
5. Bicknell JM, Carlow TJ, Kornfeld M, Stovring J, Turner P: Familial cavernous angiomas. Arch Neurol 35:746-749, 1978 (Pubitemid 9008398)
6. Bos JL: All in the family? New insights and questions regarding interconnectivity of Ras, Rap1 and Ral. EMBO J 17: 6776-6782, 1998
7. Bouffard GG, Idol JR, Braden VV, Iyer LM, Cunningham AF, Weintraub LA, et al: A physical map of human chromosome 7: an integrated YAC contig map with average STS spacing of 79 kb. Genome Res 7:673-692, 1997 (Pubitemid 27373020)
8. Cavé-Riant F, Denier C, Labauge P, Cécillon M, Maciazek J, Joutel A, et al: Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with cerebral cavernous malformations. Eur J Hum Genet 10:733-740, 2002 (Pubitemid 35460583)
9. Chang DD, Wong C, Smith H, Liu J: ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of beta1 integrin. J Cell Biol 138:1149-1157, 1997 (Pubitemid 27386463)
10. Chen L, Tanriover G, Yano H, Friedlander R, Louvi A, Gunel M: Apoptotic functions of PDCD10/CCM3, the gene mutated in cerebral cavernous malformation 3. Stroke 40:1474-1481, 2009
11. Clark JV: Familial occurrence of cavernous angiomata of the brain. J Neurol Neurosurg Psychiatry 33:871-876, 1970
12. Clatterbuck RE, Eberhart CG, Crain BJ, Rigamonti D: Ultrastructural and immunocytochemical evidence that an incompetent blood-brain barrier is related to the pathophysiology of cavernous malformations. J Neurol Neurosurg Psychiatry 71:188-192, 2001 (Pubitemid 32675143)
13. Craig HD, Günel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, et al: Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27. Hum Mol Genet 7:1851-1858, 1998 (Pubitemid 28499416)
14. Czubayko M, Knauth P, Schlüter T, Florian V, Bohnensack R: Sorting nexin 17, a non-self-assembling and a PtdIns(3)P high class affinity protein, interacts with the cerebral cavernousmalformation related protein KRIT1. Biochem Biophys Res Commun 345:1264-1272, 2006 (Pubitemid 44218788)
15. Davenport WJ, Siegel AM, Dichgans J, Drigo P, Mammi I, Pereda P, et al: CCM1 gene mutations in families segregating cerebral cavernous malformations. Neurology 56:540-543, 2001 (Pubitemid 32172885)
16. Del Curling O Jr, Kelly DL Jr, Elster AD, Craven TE: An analysis of the natural history of cavernous angiomas. J Neurosurg 75:702-708, 1991
17. Denier C, Goutagny S, Labauge P, Krivosic V, Arnoult M, Cousin A, et al: Mutations within the MGC4607 gene cause cerebral cavernous malformations. Am J Hum Genet 74: 326-337, 2004 (Pubitemid 38168620)
18. Denier C, Labauge P, Bergametti F, Marchelli F, Riant F, Arnoult M, et al: Genotype-phenotype correlations in cerebral cavernous malformations patients. Ann Neurol 60:550-556, 2006 (Pubitemid 44871797)
19. Di Rocco C, Iannelli A, Tamburrini G: Cavernous angiomas of the brain stem in children. Pediatr Neurosurg 27:92-99, 1997 (Pubitemid 28099596)
20. Dobyns WB, Michels VV, Groover RV, Mokri B, Trautmann JC, Forbes GS, et al: Familial cavernous malformations of the central nervous system and retina. Ann Neurol 21:578-583, 1987 (Pubitemid 17081193)
21. Dubovsky J, Zabramski JM, Kurth J, Spetzler RF, Rich SS, Orr HT, et al: A gene responsible for cavernous malformations of the brain maps to chromosome 7q. Hum Mol Genet 4:453-458, 1995
22. Eerola I, McIntyre B, Vikkula M: Identification of eight novel 5&πριμε;-exons in cerebral capillary malformation gene-1 (CCM1) encoding KRIT1. Biochim Biophys Acta 1517:464-467, 2001
23. Felbor U, Gaetzner S, Verlaan DJ, Vijzelaar R, Rouleau GA, Siegel AM: Large germline deletions and duplication in isolated cerebral cavernous malformation patients. Neurogenetics 8:149-153, 2007 (Pubitemid 46356248)
24. Flocks JS, Weis TP, Kleinman DC, Kirsten WH: Dose-response studies to polyoma virus in rats. J Natl Cancer Inst 35:259-284, 1965
25. Fritschi JA, Reulen HJ, Spetzler RF, Zabramski JM: Cavernous malformations of the brain stem. A review of 139 cases. Acta Neurochir (Wien) 130:35-46, 1994 (Pubitemid 24340288)
26. Gaetzner S, Stahl S, Sürücü O, Schaafhausen A, Halliger- Keller B, Bertalanffy H, et al: CCM1 gene deletion identified by MLPA in cerebral cavernous malformation. Neurosurg Rev 30:155-160, 2007
27. Gault J, Shenkar R, Recksiek P, Awad IA: Biallelic somatic and germ line CCM1 truncating mutations in a cerebral cavernous malformation lesion. Stroke 36:872-874, 2005
28. Gianfrancesco F, Esposito T, Penco S, Maglione V, Liquori CL, Patrosso MC, et al: ZPLD1 gene is disrupted in a patient with balanced translocation that exhibits cerebral cavernous malformations. Neuroscience 155:345-349, 2008
29. Gil-Nagel A, Dubovsky J, Wilcox KJ, Stewart JM, Anderson VE, Leppik IE, et al: Familial cerebral cavernous angioma: a gene localized to a 15-cM interval on chromosome 7q. Ann Neurol 39:807-810, 1996 (Erratum in Ann Neurol 39:480, 1996) (Pubitemid 26183819)
30. Gil-Nagel A, Wilcox KJ, Stewart JM, Anderson VE, Leppik IE, Rich SS: Familial cerebral cavernous angioma: clinical analysis of a family and phenotypic classification. Epilepsy Res 21:27-36, 1995
31. Giombini S, Morello G: Cavernous angiomas of the brain. Account of fourteen personal cases and review of the literature. Acta Neurochir (Wien) 40:61-82, 1978 (Pubitemid 8273172)
32. Glading A, Han J, Stockton RA, Ginsberg MH: KRIT-1/ CCM1 is a Rap1 effector that regulates endothelial cell cell junctions. J Cell Biol 179:247-254, 2007 (Pubitemid 350004889)
33. Glading AJ, Ginsberg MH: Rap1 and its effector KRIT1/ CCM1 regulate beta-catenin signaling. Dis Model Mech 3: 73-83, 2010
34. Green ED, Braden VV, Fulton RS, Lim R, Ueltzen MS, Peluso DC, et al: A human chromosome 7 yeast artificial chromosome (YAC) resource: construction, characterization, and screening. Genomics 25:170-183, 1995
35. Green ED, Green P: Sequence-tagged site (STS) content mapping of human chromosomes: theoretical considerations and early experiences. PCR Methods Appl 1:77-90, 1991
36. Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J: Corticosteroid suppression of VEGF-A in infantile hemangioma- derived stem cells. N Engl J Med 362:1005-1013, 2010
37. Günel M, Awad IA, Anson J, Lifton RP: Mapping a gene causing cerebral cavernous malformation to 7q11.2-q21. Proc Natl Acad Sci U S A 92:6620-6624, 1995
38. Gunel M, Awad IA, Finberg K, Anson JA, Steinberg GK, Batjer HH, et al: A founder mutation as a cause of cerebral cavernous malformation in Hispanic Americans. N Engl J Med 334:946-951, 1996 (Pubitemid 26114160)
39. Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, et al: KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proc Natl Acad Sci U S A 99:10677-10682, 2002
40. Guzeloglu-Kayisli O, Amankulor NM, Voorhees J, Luleci G, Lifton RP, Gunel M: KRIT1/cerebral cavernous malformation 1 protein localizes to vascular endothelium, astrocytes, and pyramidal cells of the adult human cerebral cortex. Neurosurgery 54:943-949, 2004 (Pubitemid 38437291)
41. Guzeloglu-Kayisli O, Kayisli UA, Amankulor NM, Voorhees JR, Gokce O, DiLuna ML, et al: Krev1 interaction trapped-1/ cerebral cavernous malformation-1 protein expression during early angiogenesis. J Neurosurg 100 (5 Suppl Pediatrics): 481-487, 2004
42. Hallmann R, Horn N, Selg M, Wendler O, Pausch F, Sorokin LM: Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 85:979-1000, 2005 (Pubitemid 40885221)
43. Hayman LA, Evans RA, Ferrell RE, Fahr LM, Ostrow P, Riccardi VM: Familial cavernous angiomas: natural history and genetic study over a 5-year period. Am J Med Genet 11:147-160, 1982 (Pubitemid 12222462)
44. Henkemeyer M, Rossi DJ, Holmyard DP, Puri MC, Mbamalu G, Harpal K, et al: Vascular system defects and neuronal apoptosis in mice lacking ras GTPase-activating protein. Nature 377:695-701, 1995
45. Hogan BM, Bussmann J, Wolburg H, Schulte-Merker S: Ccm1 cell autonomously regulates endothelial cellular morphogenesis and vascular tubulogenesis in zebrafish. Hum Mol Genet 17:2424-2432, 2008
46. Johnson EW, Iyer LM, Rich SS, Orr HT, Gil-Nagel A, Kurth JH, et al: Refined localization of the cerebral cavernous malformation gene (CCM1) to a 4-cM interval of chromosome 7q contained in a well-defined YAC contig. Genome Res 5: 368-380, 1995 (Pubitemid 26016743)
47. Kehrer-Sawatzki H, Wilda M, Braun VM, Richter HP, Hameister H: Mutation and expression analysis of the KRIT1 gene associated with cerebral cavernous malformations (CCM1). Acta Neuropathol 104:231-240, 2002 (Pubitemid 36082782)
48. Kere J, Ruutu T, Davies KA, Roninson IB, Watkins PC, Winqvist R, et al: Chromosome 7 long arm deletion in myeloid disorders: a narrow breakpoint region in 7q22 defined by molecular mapping. Blood 73:230-234, 1989 (Pubitemid 19040981)
49. Kidd HA, Cumings JN: Cerebral angiomata in an Icelandic family. Lancet 1:747, 1947
50. Knudson AG: Two genetic hits (more or less) to cancer. Nat Rev Cancer 1:157-162, 2001
51. Kondziolka D, Lunsford LD, Kestle JR: The natural history of cerebral cavernous malformations. J Neurosurg 83:820-824, 1995
52. Krebs LT, Xue Y, Norton CR, Shutter JR, Maguire M, Sundberg JP, et al: Notch signaling is essential for vascular morphogenesis in mice. Genes Dev 14:1343-1352, 2000 (Pubitemid 30397078)
53. Kufs H: Über heredofamiliare Angiomatose des Gehirns und der Retina, ihre Beziehungen zueinander und zur Angiomatose der Haut. Z Gesamte Neurol Psychiatr 113:651-686, 1928
54. Kurth JH, Zabramski JM, Dubovsky J: Genetic linkage of the familial cavernous malformation (CM) gene to chromosome 7q. Am J Hum Genet 55 (Suppl 3):A15, 1994 (http://www. osti.gov/energycitations/product.biblio.jsp?osti-id= 133322) [Accessed August 23, 2011]
55. Labauge P, Laberge S, Brunereau L, Levy C, Tournier- Lasserve E: Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families. Société Française de Neurochirurgie. Lancet 352:1892-1897, 1998 (Pubitemid 28561250)
56. Laberge S, Labauge P, Maréchal E, Maciazek J, Tournier- Lasserve E: Genetic heterogeneity and absence of founder effect in a series of 36 French cerebral cavernous angiomas families. Eur J Hum Genet 7:499-504, 1999 (Pubitemid 29261336)
57. Laberge-le Couteulx S, Jung HH, Labauge P, Houtteville JP, Lescoat C, Cecillon M, et al: Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat Genet 23:189-193, 1999 (Pubitemid 29455391)
58. Liquori CL, Berg MJ, Siegel AM, Huang E, Zawistowski JS, Stoffer T, et al: Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations. Am J Hum Genet 73: 1459-1464, 2003 (Pubitemid 38037437)
59. Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, et al: Deletions in CCM2 are a common cause of cerebral cavernous malformations. Am J Hum Genet 80:69-75, 2007 (Pubitemid 46047651)
60. Liquori CL, Berg MJ, Squitieri F, Ottenbacher M, Sorlie M, Leedom TP, et al: Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus. Hum Mutat 27:118, 2006
61. Liquori CL, Penco S, Gault J, Leedom TP, Tassi L, Esposito T, et al: Different spectra of genomic deletions within the CCM genes between Italian and American CCM patient cohorts. Neurogenetics 9:25-31, 2008
62. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al: Heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 121:e46-e215, 2010 (Erratum in Circulation 121: e260, 2010)
63. Lonjon M, Roche JL, George B, Mourier KL, Paquis P, Lot G, et al: [Intracranial cavernoma. 30 cases.] Presse Med 22: 990-994, 1993 (Fr)
64. Lucas M, Costa AF, García-Moreno JM, Solano F, Gamero MA, Izquierdo G: Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene. BMC Neurol 3:5, 2003
65. Lucas M, Costa AF, Montori M, Solano F, Zayas MD, Izquierdo G: Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations. Ann Neurol 49:529-532, 2001 (Pubitemid 32281339)
66. Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, et al: PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Mol Biol Cell 18:1965-1978, 2007 (Pubitemid 46911350)
67. Mably JD, Chuang LP, Serluca FC, Mohideen MA, Chen JN, Fishman MC: Santa and valentine pattern concentric growth of cardiac myocardium in the zebrafish. Development 133:3139-3146, 2006 (Pubitemid 44404337)
68. Marchuk DA, Gallione CJ, Morrison LA, Clericuzio CL, Hart BL, Kosofsky BE, et al: A locus for cerebral cavernous malformations maps to chromosome 7q in two families. Genomics 28:311-314, 1995
69. Mason I, Aase JM, Orrison WW, Wicks JD, Seigel RS, Bicknell JM: Familial cavernous angiomas of the brain in an Hispanic family. Neurology 38:324-326, 1988 (Pubitemid 18036866)
70. Matos P, Skaug J, Marques B, Beck S, Veríssimo F, Gespach C, et al: Small GTPase Rac1: structure, localization, and expression of the human gene. Biochem Biophys Res Commun 277: 741-751, 2000
71. McCormick WF: The pathology of vascular ("arteriovenous") malformations. J Neurosurg 24:807-816, 1966
72. Michael JC, Levin PM: Multiple telangiectases of the brain: a discussion of hereditary factors in their development. Arch Neurol Psychiatry 36:514-529, 1936
73. Moriarity JL, Wetzel M, Clatterbuck RE, Javedan S, Sheppard JM, Hoenig-Rigamonti K, et al: The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 44:1166-1173, 1999 (Pubitemid 29252736)
74. Moussa R, Harb A, Menassa L, Risk T, Nohra G, Samaha E, et al: [Etiologic spectrum of intracerebral hemorrhage in young patients.] Neurochirurgie 52 (2-3 Pt 1):105-109, 2006 (Fr)
75. Nibert M, Heim S: Uterine leiomyoma cytogenetics. Genes Chromosomes Cancer 2:3-13, 1990
76. Otten P, Pizzolato GP, Rilliet B, Berney J: [131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies.] Neurochirurgie 35:82-83, 128-131, 1989 (Fr)
77. Pagenstecher A, Stahl S, Sure U, Felbor U: A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells. Hum Mol Genet 18:911-918, 2009
78. Pizon V, Chardin P, Lerosey I, Olofsson B, Tavitian A: Human cDNAs rap1 and rap2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the 'effector'region. Oncogene 3:201-204, 1988
79. Plummer NW, Gallione CJ, Srinivasan S, Zawistowski JS, Louis DN, Marchuk DA: Loss of p53 sensitizes mice with a mutation in Ccm1 (KRIT1) to development of cerebral vascular malformations. Am J Pathol 165:1509-1518, 2004 (Pubitemid 39435151)
80. Plummer NW, Squire TL, Srinivasan S, Huang E, Zawistowski JS, Matsunami H, et al: Neuronal expression of the Ccm2 gene in a new mouse model of cerebral cavernous malformations. Mamm Genome 17:119-128, 2006 (Pubitemid 43209151)
81. Porter PJ, Willinsky RA, Harper W, Wallace MC: Cerebral cavernous malformations: natural history and prognosis after clinical deterioration with or without hemorrhage. J Neurosurg 87:190-197, 1997 (Pubitemid 27349102)
82. Reedquist KA, Ross E, Koop EA, Wolthuis RM, Zwartkruis FJ, van Kooyk Y, et al: The small GTPase, Rap1, mediates CD31-induced integrin adhesion. J Cell Biol 148:1151-1158, 2000
83. Rigamonti D, Hadley MN, Drayer BP, Johnson PC, Hoenig- Rigamonti K, Knight JT, et al: Cerebral cavernous malformations. Incidence and familial occurrence. N Engl J Med 319: 343-347, 1988
84. Robinson JR, Awad IA, Little JR: Natural history of the cavernous angioma. J Neurosurg 75:709-714, 1991
85. Ruggieri R, Bender A, Matsui Y, Powers S, Takai Y, Pringle JR, et al: RSR1, a ras-like gene homologous to Krev-1 (smg21A/rap1A): role in the development of cell polarity and interactions with the Ras pathway in Saccharomyces cerevisiae. Mol Cell Biol 12:758-766, 1992
86. Russell DS, Rubinstein LJ: Pathology of Tumours of the Nervous System. London: E. Arnold, 1989, pp 730-736
87. Sahoo T, Goenaga-Diaz E, Serebriiskii IG, Thomas JW, Kotova E, Cuellar JG, et al: Computational and experimental analyses reveal previously undetected coding exons of the KRIT1 (CCM1) gene. Genomics 71:123-126, 2001 (Pubitemid 32097210)
88. Sahoo T, Johnson EW, Thomas JW, Kuehl PM, Jones TL, Dokken CG, et al: Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1). Hum Mol Genet 8:2325-2333, 1999 (Pubitemid 29525349)
89. Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G: Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30:e57, 2002
90. Sedgwick SG, Smerdon SJ: The ankyrin repeat: a diversity of interactions on a common structural framework. Trends Biochem Sci 24:311-316, 1999 (Pubitemid 29366805)
91. Seker A, Pricola KL, Guclu B, Ozturk AK, Louvi A, Gunel M: CCM2 expression parallels that of CCM1. Stroke 37:518-523, 2006 (Pubitemid 43732017)
92. Serebriiskii I, Estojak J, Sonoda G, Testa JR, Golemis EA: Association of Krev-1/rap1a with Krit1, a novel ankyrin repeatcontaining protein encoded by a gene mapping to 7q21-22. Oncogene 15:1043-1049, 1997 (Pubitemid 27401958)
93. Simard JM, Garcia-Bengochea F, Ballinger WE Jr, Mickle JP, Quisling RG: Cavernous angioma: a review of 126 collected and 12 new clinical cases. Neurosurgery 18:162-172, 1986 (Pubitemid 16161278)
94. Stahl S, Gaetzner S, Voss K, Brackertz B, Schleider E, SürücüO, et al: Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex. Hum Mutat 29:709-717, 2008 (Pubitemid 351614596)
95. Stockton RA, Shenkar R, Awad IA, Ginsberg MH: Cerebral cavernous malformations proteins inhibit Rho kinase to stabilize vascular integrity. J Exp Med 207:881-896, 2010
96. Tanriover G, Boylan AJ, Diluna ML, Pricola KL, Louvi A, Gunel M: PDCD10, the gene mutated in cerebral cavernous malformation 3, is expressed in the neurovascular unit. Neurosurgery 62:930-938, 2008
97. Tomlinson FH, Houser OW, Scheithauer BW, Sundt TM Jr, Okazaki H, Parisi JE: Angiographically occult vascular malformations: a correlative study of features on magnetic resonance imaging and histological examination. Neurosurgery 34: 792-800, 1994 (Pubitemid 24130056)
98. Uhlik MT, Abell AN, Johnson NL, Sun W, Cuevas BD, Lobel-Rice KE, et al: Rac-MEKK3-MKK3 scaffolding for p38 MAPK activation during hyperosmotic shock. Nat Cell Biol 5:1104-1110, 2003 (Pubitemid 37509118)
99. Verlaan DJ, Siegel AM, Rouleau GA: Krit1 missense mutations lead to splicing errors in cerebral cavernous malformation. Am J Hum Genet 70:1564-1567, 2002 (Pubitemid 34533903)
100. Voigt K, Yaşargil MG: Cerebral cavernous haemangiomas or cavernomas. Incidence, pathology, localization, diagnosis, clinical features and treatment. Review of the literature and report of an unusual case. Neurochirurgia (Stuttg) 19:59-68, 1976
101. Voss K, Stahl S, Schleider E, Ullrich S, Nickel J, Mueller TD, et al: CCM3 interacts with CCM2 indicating common pathogenesis for cerebral cavernous malformations. Neurogenetics 8:249-256, 2007 (Pubitemid 47624455)
102. Wang HU, Chen ZF, Anderson DJ: Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93:741-753, 1998 (Pubitemid 28257581)
103. Wang Y, Liu H, Zhang Y, Ma D: cDNA cloning and expression of an apoptosis-related gene, humanTFAR15 gene. Sci China C Life Sci 42:323-329, 1999
104. Wernig F, Mayr M, Xu Q: Mechanical stretch-induced apoptosis in smooth muscle cells is mediated by beta1-integrin signaling pathways. Hypertension 41:903-911, 2003 (Pubitemid 36418464)
105. Whitehead KJ, Chan AC, Navankasattusas S, Koh W, London NR, Ling J, et al: The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat Med 15:177-184, 2009 (Erratum in Nat Med 15:462, 2009)
106. Whitehead KJ, Plummer NW, Adams JA, Marchuk DA, Li DY: Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Development 131: 1437-1448, 2004 (Pubitemid 38443895)
107. Wienecke R, Maize JC Jr, Reed JA, de Gunzburg J, Yeung RS, DeClue JE: Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues. Am J Pathol 150:43-50, 1997 (Pubitemid 27027094)
108. Wojnowski L, Zimmer AM, Beck TW, Hahn H, Bernal R, Rapp UR, et al: Endothelial apoptosis in Braf-deficient mice. Nat Genet 16:293-297, 1997 (Pubitemid 27280215)
109. Wong JH, Awad IA, Kim JH: Ultrastructural pathological features of cerebrovascular malformations: a preliminary report. Neurosurgery 46:1454-1459, 2000 (Pubitemid 32037675)
110. Zabramski JM, Wascher TM, Spetzler RF, Johnson B, Golfinos J, Drayer BP, et al: The natural history of familial cavernous malformations: results of an ongoing study. J Neurosurg 80: 422-432, 1994 (Pubitemid 24073002)
111. Zawistowski JS, Serebriiskii IG, Lee MF, Golemis EA, Marchuk DA: KRIT1 association with the integrin-binding protein ICAP- 1: a new direction in the elucidation of cerebral cavernous malformations (CCM1) pathogenesis. Hum Mol Genet 11: 389-396, 2002 (Pubitemid 34213612)
112. Zawistowski JS, Stalheim L, Uhlik MT, Abell AN, Ancrile BB, Johnson GL, et al: CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum Mol Genet 14:2521-2531, 2005 (Pubitemid 41236065)
113. Zhang J, Clatterbuck RE, Rigamonti D, Chang DD, Dietz HC: Interaction between krit1 and icap1alpha infers perturbation of integrin beta1-mediated angiogenesis in the pathogenesis of cerebral cavernous malformation. Hum Mol Genet 10:2953-2960, 2001 (Pubitemid 34030926)
114. Zhang J, Clatterbuck RE, Rigamonti D, Dietz HC: Cloning of the murine Krit1 cDNA reveals novel mammalian 5′ coding exons. Genomics 70:392-395, 2000 (Pubitemid 32095439)