Germline mutations in the CCM1 gene, encoding Krit1, cause cerebral cavernous malformations.
Mutations in the Kritl gene have been recently discovered as the cause of hereditary cerebral cavernous angioma. We sought the possibility that de novo, noninherited mutations of Kritl also cause cavernous angioma. A patient with two cerebral malformations carries a heterozygous deletion of two base pairs (741delTC) in exon VI of the Kritl gene. The deletion initiates a frameshift mutation that, 23 amino acids downstream, encodes a TAA stop triplet replacing a CAT triplet of histidine at exon VII (H271X). Magnetic resonance images of the parents were normal, neither parent carries the 741delTC mutation, and both bear the wild-type sequence of exon VI. These findings document a de novo germline mutation in Kritl gene that causes cerebral cavernous malformations.
Lucas
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M
Servicio de Biología Molecular, Hospital Universitario Virgen Macarena, Seville, Spain. lucas@cica.es
Costa
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Montori
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Solano
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D001932:Brain Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D018095:Germ-Line Mutation / Q000235:genetics*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000075927:KRIT1 Protein; D008279:Magnetic Resonance Imaging; D008780:Methyltransferases / Q000235:genetics*; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D008780:Methyltransferases; C055097:mRNA (guanine(N7))-methyltransferase