Germline mutations in theCCM1 gene, encoding Krit1, cause cerebral cavernous malformations

2001 ◽  
Vol 49 (4) ◽  
pp. 529-532 ◽  
Author(s):  
Miguel Lucas ◽  
Alzenira F. Costa ◽  
Mariano Montori ◽  
Francisca Solano ◽  
Mar�a D. Zayas ◽  
...  
Keyword(s):  
Germline Mutations ◽  
Cerebral Cavernous Malformations ◽  
Gene Encoding ◽  
Cavernous Malformations

scholarly journals Mutations in a Gene Encoding a Novel Protein Containing a Phosphotyrosine-Binding Domain Cause Type 2 Cerebral Cavernous Malformations

2003 ◽  
Vol 73 (6) ◽  
pp. 1459-1464 ◽  
Author(s):  
Christina L. Liquori ◽  
Michel J. Berg ◽  
Adrian M. Siegel ◽  
Elizabeth Huang ◽  
Jon S. Zawistowski ◽  
...  
Keyword(s):  
Binding Domain ◽  
Cerebral Cavernous Malformations ◽  
Gene Encoding ◽  
Cavernous Malformations ◽  
Phosphotyrosine Binding Domain ◽  
Novel Protein

scholarly journals Biallelic somatic and germline mutations in cerebral cavernous malformations (CCMs): evidence for a two-hit mechanism of CCM pathogenesis

2008 ◽  
Vol 18 (5) ◽  
pp. 919-930 ◽  
Author(s):  
Amy L. Akers ◽  
Eric Johnson ◽  
Gary K. Steinberg ◽  
Joseph M. Zabramski ◽  
Douglas A. Marchuk
Keyword(s):  
Germline Mutations ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

scholarly journals Mutations in the Gene Encoding KRIT1, a Krev-1/rap1a Binding Protein, Cause Cerebral Cavernous Malformations (CCM1)

1999 ◽  
Vol 8 (12) ◽  
pp. 2325-2333 ◽  
Author(s):  
T. Sahoo ◽  
E. W. Johnson ◽  
J. W. Thomas ◽  
P. M. Kuehl ◽  
T. L. Jones ◽  
...  
Keyword(s):  
Binding Protein ◽  
Cerebral Cavernous Malformations ◽  
Gene Encoding ◽  
Cavernous Malformations

scholarly journals A Series of 14 Representative Presentations of Cerebral Cavernous Malformations

2021 ◽  
pp. 101298
Author(s):  
Ryan Hudnall ◽  
Eric X. Chen ◽  
Patrick J Opperman ◽  
Sean Kelly ◽  
Justin A. Cramer ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

scholarly journals A transcription-based mechanism for oncogenic β-catenin-induced lethality in BRCA1/2-deficient cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rebecca A. Dagg ◽  
Gijs Zonderland ◽  
Emilia Puig Lombardi ◽  
Giacomo G. Rossetti ◽  
Florian J. Groelly ◽  
...  
Keyword(s):  
Dna Damage ◽  
Replication Fork ◽  
High Throughput Sequencing ◽  
Germline Mutations ◽  
Cdk Inhibitor ◽  
Rna Seq ◽  
Gene Encoding ◽  
Origin Firing ◽  
Replication Fork Progression ◽  
Transcriptional Alterations

AbstractBRCA1 or BRCA2 germline mutations predispose to breast, ovarian and other cancers. High-throughput sequencing of tumour genomes revealed that oncogene amplification and BRCA1/2 mutations are mutually exclusive in cancer, however the molecular mechanism underlying this incompatibility remains unknown. Here, we report that activation of β-catenin, an oncogene of the WNT signalling pathway, inhibits proliferation of BRCA1/2-deficient cells. RNA-seq analyses revealed β-catenin-induced discrete transcriptome alterations in BRCA2-deficient cells, including suppression of CDKN1A gene encoding the CDK inhibitor p21. This accelerates G1/S transition, triggering illegitimate origin firing and DNA damage. In addition, β-catenin activation accelerates replication fork progression in BRCA2-deficient cells, which is critically dependent on p21 downregulation. Importantly, we find that upregulated p21 expression is essential for the survival of BRCA2-deficient cells and tumours. Thus, our work demonstrates that β-catenin toxicity in cancer cells with compromised BRCA1/2 function is driven by transcriptional alterations that cause aberrant replication and inflict DNA damage.

Genotype-phenotype correlations in cerebral cavernous malformations patients

2006 ◽  
Vol 60 (5) ◽  
pp. 550-556 ◽  
Author(s):  
Christian Denier ◽  
Pierre Labauge ◽  
Françoise Bergametti ◽  
Florence Marchelli ◽  
Florence Riant ◽  
...  
Keyword(s):  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations

Abstract 159: Exceptional Aggressiveness of CCM3 Phenotype

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tania J Rebeiz ◽  
Abdul Ghani Mikati ◽  
Darlene Simkhin ◽  
Cornelia Lee ◽  
Amy Akers ◽  
...  
Keyword(s):  
Spontaneous Mutation ◽  
Mutation Screening ◽  
High Sensitivity ◽  
Skin Lesions ◽  
Cerebral Cavernous Malformations ◽  
Cognitive Disability ◽  
Cavernous Malformations ◽  
Patient Advocacy Group ◽  
Sporadic Cases

Introduction: Familial forms of cerebral cavernous malformations (CCM) account for about 1/3 of cases, involving autosomal dominant inheritance at 1 of 3 gene loci. Few studies have examined any special features of the rarest cases with CCM3 (PDCD10 ) mutation at q3, constituting <15 % of probands genotyped by sequential mutation screening, and <2% of CCM cases at large. Hypothesis: We hypothesize that CCM3 cases have unique phenotypic features not recognized in the more common CCM1 and 2 families, or in sporadic cases. Methods: Twelve probands including 17 subjects with confirmed CCM3 mutations were prospectively enrolled through systematic facilitated referral by the patient advocacy group Angioma Alliance. Clinical features were catalogued, including high sensitivity susceptibility weighted imaging (SWI). Rates of overt hemorrhage were determined based on adjudicated criteria. Comparisons were made to systematic literature review of natural history data on non-CCM3 cases. Results: The first overt hemorrhage occurred most often in the 1st decade of life (mean age 5.8). Nine of 17 subjects (52%) suffered 30 overt hemorrhages, with an estimated incidence of 6.7 % /patient/year based on exposure risk since birth, and 17% /patient/year based on risk since first symptom onset. Lesion burden on SWI was exceptionally high, >100 lesions in 28%, and > 20 lesions in 72% of cases, respectively. Adjusted bleed rate was <0.5% /lesion/year. New SWI lesions formed at a rate of 2.7/patient/year in prospective follow-up, and 1.8/patient/year based on years since birth. Scoliosis was found in 47% (an association not recognized previously), skin lesions in 29.4%, and brain tumors in 29.4% of cases, respectively. Cognitive disability affected 47% of cases, mostly in association with high lesion burden. Six of 15 cases with parental screening (40%) represented a spontaneous mutation. Conclusion: CCM3 is exceptionally aggressive compared to other familial and sporadic CCM. High risks of bleeding and cognitive disability mostly reflect severe lesion burden early in life, rather than a higher risk per lesion. These results will inform the design of clinical trials, urgently needed to address this unique CCM cohort.

scholarly journals Loss of CCM3 impairs DLL4-Notch signalling: implication in endothelial angiogenesis and in inherited cerebral cavernous malformations

2013 ◽  
Vol 17 (3) ◽  
pp. 407-418 ◽  
Author(s):  
Chao You ◽  
Ibrahim Erol Sandalcioglu ◽  
Philipp Dammann ◽  
Ute Felbor ◽  
Ulrich Sure ◽  
...  
Keyword(s):  
Notch Signalling ◽  
Cerebral Cavernous Malformations ◽  
Cavernous Malformations
Sign in / Sign up

Export Citation Format

Share Document