Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families

Labauge, Pierre; Laberge, Sophie; Brunereau, L.; Levy, C.D.P.; Tournier‐Lasserve, Elisabeth

doi:10.1016/s0140-6736(98)03011-6

Cited by 233 publications

(182 citation statements)

References 20 publications

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“…4 A mutation was previously identified in 12 of them. 8 Detailed clinical and neuroimaging informations were collected for all patients through direct interview and reviewing of medical charts.…”

Section: Patientsmentioning

confidence: 99%

“…On the contrary, familial CCM are characterised by a high frequency of multiple lesions, whose number is strongly correlated to patients' age suggesting a dynamic nature of these lesions. 4 'Sporadic' cases harbouring multiple lesions have been shown to be in reality affected by an hereditary form of the disease since 75% of them have an asymptomatic parent with CCM lesions on brain MRI, due to incomplete clinical penetrance of this condition. 4 De novo mutation of KRIT1/CCM1 gene has also been reported in one CCM patient with multiple lesions.…”

Section: Introductionmentioning

confidence: 99%

“…4 'Sporadic' cases harbouring multiple lesions have been shown to be in reality affected by an hereditary form of the disease since 75% of them have an asymptomatic parent with CCM lesions on brain MRI, due to incomplete clinical penetrance of this condition. 4 De novo mutation of KRIT1/CCM1 gene has also been reported in one CCM patient with multiple lesions. 5 Three CCM loci had been previously identified on 7q (CCM1), 7p (CCM2) and 3q (CCM3).…”

Section: Introductionmentioning

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: Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Cavernous hemangioma is known to occur as sporadic and familial types. 15) A series of 8131 MR images showed 32 patients (0.4%) met the MR imaging criteria of cavernous angioma. 3) This low incidence and exclusion of patients with a familial history of cavernous hemangioma indicate that patients with cavernous hemangioma were unlikely in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…2,23) T 2 *-weighted gradient echo MR imaging is superior to other conventional imaging methods for the detection of small hemorrhagic lesions, because the T 2 * is shortened by heterogeneity in a magnetic susceptibility-induced static field arising from paramagnetic blood breakdown products. 1,15) The present study investigated the relationship between hypertensive intracerebral hemorrhage and minute hemorrhage in patients with hypertension.…”

Section: Introductionmentioning

confidence: 98%

Relationship Between Stroke and Asymptomatic Minute Hemorrhages in Hypertensive Patients.

Yanagawa

Sakamoto

Okada

et al. 2001

Neurol. Med. Chir.(Tokyo)

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Value of Gradient-Echo Magnetic Resonance Imaging in the Diagnosis of Familial Cerebral Cavernous Malformation

Lehnhardt¹,

Smekal²,

Rückriem³

et al. 2005

Arch Neurol

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Background: Cerebral cavernous malformations (CCMs) are congenital vascular anomalies that can cause seizures, intracranial hemorrhages, focal neurological deficits, and migrainelike headaches. Magnetic resonance (MR) imaging has substantially facilitated diagnosis of CCM. It is now widely accepted that familial clustering with an autosomal dominant inheritance pattern should be suspected in cases of multiple lesions. Objective: To determine by MR imaging the penetrance of cavernous malformations in a 3-generation family that included 5 members with typical clinical signs and diagnostic findings. Methods: All family members underwent routine MR T1-weighted and T2-weighted spin-echo sequences in addition to MR T2-weighted gradient-echo sequences. Results: Four family members had been symptomatic with either brainstem bleeding, headaches, or focal neurological signs. The gradient-echo sequences yielded a dramatically higher sensitivity with regard to lesion number and distribution. As in previous reports of familial CCM, an increase in lesion number with increasing age, changes in lesion characteristics, de novo occurrence in serial MR imaging over time, and the phenomenon of anticipation could be confirmed in this family. Conclusion: Magnetic resonance gradient-echo sequences should be considered the method of choice for diagnosis of familial CCM.

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Hereditary cerebral cavernous angiomas: clinical and genetic features in 57 French families

Cited by 233 publications

References 20 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

Relationship Between Stroke and Asymptomatic Minute Hemorrhages in Hypertensive Patients.

Value of Gradient-Echo Magnetic Resonance Imaging in the Diagnosis of Familial Cerebral Cavernous Malformation

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