Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27

Craig, Holly Duncan; Günel, Murat; Cepeda, Obed; Johnson, Eric W.; Ptáček, Louis J.; Steinberg, Gary K.; Ogilvy, Christopher S.; Berg, Michel J.; Crawford, Steve; Scott, R. Michael; Steichen-Gersdorf, Elisabeth; Sabroe, R.A.; Kennedy, C. T. C.; Mettler, Gabrielle; Beis, M; Fryer, Alan; Awad, Issam A.; Lifton, Richard P.

doi:10.1093/hmg/7.12.1851

Cited by 316 publications

(210 citation statements)

References 23 publications

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“…7 However, this proportion is most likely underestimated for several reasons. Based on the strategy that we have used, we may have missed deletions of KRIT1 (however, KRIT1 deletions have not been reported so far), and we may also have missed KRIT1 point mutations due to incomplete SSCP sensitivity.…”

Section: Discussionmentioning

confidence: 99%

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Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations

et al. 2002

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Cerebral Cavernous Malformations (CCM/MIM 604214) are vascular malformations characterised by abnormally enlarged capillary cavities without intervening brain parenchyma. Clinical manifestations include seizures, cerebral haemorrhages and focal neurological deficits. They occur as a sporadic or autosomal dominant condition. Most often, sporadic cases have only one lesion and familial cases are characterised by a high frequency of multiple lesions. Three CCM loci were previously mapped on 7q (CCM1), 7p (CCM2) and 3q (CCM3) and CCM1 gene was identified as coding Krit1, a protein of unknown function, which was shown initially to interact in yeast two hybrid assays with Rap1A, a small ras GTPase and more recently to Icap1a, a modulator of b1 integrin signal transduction. Herein, we screened KRIT1 gene in 121 unrelated, consecutively recruited, CCM probands having at least one affected relative and/ or showing multiple lesions on cerebral MRI. Fifty-two of these probands (43%) were shown to carry a KRIT1 mutation. Forty-two distinct mutations were identified including six recurrent ones. Three-quarters of these mutations were located in the C-terminal half of the gene, mostly within exons 13, 15 and 17. All of them are predicted to lead to a premature stop codon. No missense mutation was identified. The only two nucleotide substitutions predicted to be missense mutations led in fact to an abnormal splicing and a premature stop codon. Altogether these data suggest that KRIT1 mRNA decay due to the presence of premature stop codons and Krit1 haploinsufficiency may be the underlying mechanism of CCM.

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Section: Discussionmentioning

confidence: 99%

“…5 Three CCM loci had been previously identified on 7q (CCM1), 7p (CCM2) and 3q (CCM3). 6,7 Recently, CCM1 was identified as the KRIT1 gene. 8,9 KRIT1, a protein of unknown function so far, was previously identified through a yeast two-hybrid screen designed to identify proteins interacting with Rap1A, a small Ras like GTPase protein.…”

Section: Introductionmentioning

confidence: 99%

Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations

et al. 2002

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“…Quando familiar são mais comumente diagnosticados na população hispano-americana, com caráter autossômico dominante e geralmente múl-tiplos, o primeiro gene (CCM1) sendo mapeado no braço longo do cromossomo 7 (7q11.2q21) 25,26 e outros dois no braço curto do cromossomo 7 (7p15- 13) e no braço longo do cromossomo 3 (3q25. 27 . Devido a algumas de suas características como tamanho, lesões múltiplas e localização podem, apesar de serem lesões benignas, apresentar risco elevado de morbidade 18 .…”

Section: Discussionunclassified

Cavernoma gigante: relato de dois casos

Andrade

Prandini

Braga

2002

Arq. Neuro-Psiquiatr.

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RESUMO -Angiomas cavernosos ou hemangiomas ou ainda cavernomas são malformações do sistema nervoso central, classificadas como lesões cerebrais vasculares ocultas, frequentemente assintomáticas, sendo relativamente raras. Definidas histologicamente como massas compactas cavernosas ou canais sinusoidais de vários tamanhos, com paredes finas no interior do parênquima cerebral e sem intervenção do tecido glial. Podem ocorrer em qualquer faixa etária inclusive em neonatos. Na maioria das vezes são lesões de tamanho reduzido, localizadas no interior do parênquima encefálico. Angiograficamente não mostram alterações com circulação patológica, podendo mesmo não ser diagnosticados pela tomografia, sendo o exame ideal para o seu diagnóstico a ressonância magnética de crânio. Os cavernomas são lesões histologicamente benignas mas, dependendo de sua localização, podem trazer grandes transtornos neurológicos e ser irressecáveis. A exérese cirúrgica da lesão é o tratamento de escolha se a lesão for única e em localização favorável e estiver desencadeando sintomatologia neurológica prejudicial ao paciente. Apresentamos dois casos de cavernomas gigantes que apresentaram boa evolução após ressecção cirúrgica completa. Descritos como gigantes, foram encontrados apenas três casos individuais na literatura .PALAVRAS-CHAVES: cavernoma, angioma cavernoso gigante.Giant cavernous angioma: report of two cases Giant cavernous angioma: report of two cases Giant cavernous angioma: report of two cases Giant cavernous angioma: report of two cases Giant cavernous angioma: report of two cases ABSTRACT -Cavernous angiomas or haemangiomas or yet cavernomas are malformations of the central nervous system classified as occult vascular brain lesions. These rare lesions are clinically silent. They are defined by the presence of abnormally large vascular cavities or sinusoids channels of variable size, with sharp walls, located inside but not invading the brain parenchyma. They can occur at any age, including the neonatal period. Most of the small lesions are located inside the brain parenchyma. No abnormal circulation can be demonstrated in angiography and CT scan can be helpful for diagnosis only in rare occasions. Magnetic resonance is the best exam to demonstrate the lesion. Despite the benign character some lesions may cause neurologic dysfunction when their removal may be difficult. Complete extirpation is the best treatment if the lesion is favorable located and is causing neurological dysfunction. Two cases of giant cavernomas with good outcome after total removal are present. Only three cases of giant cavernomas were reported in the literature.KEY WORDS: cavernoma, giant cavernous angioma.Cavernomas intracerebrais são malformações vasculares raras, angiograficamente ocultas 1 , com características histopatológicas próprias e distintas de outras malformações vasculares cerebrais (Tabela 1) 2 . De acordo com Russel e Rubinstein 3 , 75% são supratentoriais, podendo acometer qualquer lobo do cé-rebro. Apresentam localização preferencial na regi...

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“…Kromozomun q11-q22 lokusunda yer alan ve SKM'nun ailesel formlarında ilk bulunan gendir (8). CCM1'in ürünü olan KRIT1; RAS protein ailesine ait bir GTPaz olan RAP1A ile etkileşen ve ankirin tekrarlı yapı barındıran bir proteindir (9,10).…”

Section: Skm Oluşumundan Sorumlu Genler Ccm1 (Krit1)unclassified

“…Bunlar; KRIT1 (KREV1-RAP1A interaction trapped-1 veya CCM1) kromozom 7q, CCM2 (OSM veya Osmo-sensing scaffold for MEKK3) kromozom 7p ve PDCD10 (Programmed cell death 10 veya CCM3) kromozom 3q genleridir. Yapılan bağlantı (linkaj) analizleri sonucunda bu genlerden en çok CCM1'in etkin rol oynadığı ancak diğer iki genin de buna eşlik ederek hareket ettiği vurgulanmaktadır (8).…”

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Molecular and Genetic Basis of Cerebral Cavernous Malformations

Cici¹,

Dilmaç²,

Tanrıöver³

2017

Akd Med J

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ÖZAmaç: Serebral kavernöz malformasyonlar (SKM) santral sinir sisteminde ölümcül hemorajik inmelere ve fokal nörolojik sorunlara neden olma eğilimi gösteren damarsal lezyonlardır. Bu malformasyonlar, ilgili genlerinden birisinde oluşacak fonksiyon kaybı mutasyonlarıyla ortaya çıkmakta olup; büyük çoğunlukta sporadik olmasına rağmen ailesel kalıtımla da ortaya çıktığı genetik çalışmaların sonuçlarıyla da belirtilmektedir. Gereç ve Material and Methods:The aim of the study was to determine the molecular and genetic basis of CCMs and their known roles in cells.

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Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27

Cited by 316 publications

References 23 publications

Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations

Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with Cerebral Cavernous Malformations

Cavernoma gigante: relato de dois casos

Molecular and Genetic Basis of Cerebral Cavernous Malformations

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