title: Cutaneous venous malformations in familial cerebral cavernomatosis caused by KRIT1 gene mutations.
abstract: BACKGROUND
  Cerebral cavernous malformations (CCMs) are vascular lesions characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. Although often asymptomatic, seizures, cerebral haemorrhages and focal neurological deficits are well-documented complications. Mutations in the CCM1 (7q21-22), CCM2 (7p13-15) and CCM3 (3q25.2-27) genes have been identified in familial CCM. In rare instances, the association of congenital hyperkeratotic cutaneous capillary-venous malformations (HCCVMs) with CCM1 has been reported.
  
  
  METHODS
  We studied 6 members of a family with CCMs. Four members of the family developed late-onset multiple, tiny, bluish, soft, cutaneous papules, mainly located on the face, arm and abdominal area, corresponding histologically to venous malformations. A splice donor site mutation in intron 4 (c. 1146 + 1 G-->A) in the CCM1 gene was identified.
  
  
  CONCLUSIONS
  Our findings suggest that mutations in the KRIT1 gene may cause phenotypically heterogeneous cutaneous vascular lesions other than those previously described as HCCVMs.
authors.affiliation: Department of Dermatology, Hospital del Mar, IMAS, Barcelona ES-08003, Spain. 93828@imas.imim.es
authors.forename: Agustí
authors.initials: A
authors.lastname: Toll
authors.forename: Elisabet
authors.initials: E
authors.lastname: Parera
authors.forename: Ana M
authors.initials: AM
authors.lastname: Giménez-Arnau
authors.forename: Alejandro
authors.initials: A
authors.lastname: Pou
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: Nisha
authors.initials: N
authors.lastname: Limaye
authors.forename: Miikka
authors.initials: M
authors.lastname: Vikkula
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Pujol
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics*; D020785:Central Nervous System Vascular Malformations / Q000150:complications / Q000235:genetics*; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000150:complications / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017445:Skin Diseases, Vascular / Q000150:complications / Q000235:genetics* / Q000473:pathology; D054079:Vascular Malformations / Q000150:complications / Q000235:genetics* / Q000473:pathology; D014680:Veins / Q000002:abnormalities
chemical_list: D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins