CCM3 Mutations Are Associated with Early-Onset Cerebral Hemorrhage and Multiple Meningiomas

Molecular Syndromology

H.-D. Fournier¹  P. Lejeune¹  C. Bernreuther¹  M. Cecillon¹  S. Michalak-Provost¹  H. Hosseini¹  P. Labauge¹  G. Boulday¹  E. Tournier-Lasserve¹  F. Chapon¹  F. Riant¹  C. Choe¹  M. Orth¹  F. Bergametti¹  C. Denier¹ 

[1] aService de Génétique Neuro-Vasculaire, Assistance Publique-Hôpitaux de Paris, Paris, France

关键词: Cavernous angioma;    CCM;    CCM1;    CCM2;    KRIT1;    Meningioma;    PDCD10
;   

DOI  :  10.1159/000350042

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Mutations of CCM3/PDCD10 cause 10-15% of hereditary cerebral cavernous malformations. The phenotypic characterization of CCM3-mutated patients has been hampered by the limited number of patients harboring a mutation in this gene. This is the first report on molecular and clinical features of a large cohort of CCM3 patients. Molecular screening for point mutations and deletions was used to identify 54 CCM3-mutated index patients. Age at referral and clinical onset, type of inaugural events and presence of extra-axial lesions were investigated in these 54 index patients and 22 of their mutated relatives. Mean age at clinical onset was 23.0 ± 16 years. Clinical onset occurred before 10 years in 26% of the patients, and cerebral hemorrhage was the initial presentation in 72% of these patients. Multiple extra-axial, dural-based lesions were detected in 7 unrelated patients. These lesions proved to be meningiomas in 3 patients who underwent neurosurgery and pathological examination. This ‘multiple meningiomas’ phenotype is not associated with a specific CCM3 mutation. Hence, CCM3 mutations are associated with a high risk of early-onset cerebral hemorrhage and with the presence of multiple meningiomas.

【 授权许可】

Unknown