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BMC Neurol. 2003 Jul 23;3:5. Epub 2003 Jul 23.

Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene.

Author information

1
Molecular Biology Services of the Virgen Macarena University Hospital, Avda Dr, Fedriani sn, 41009 Sevilla, Spain. lucas@us.es

Abstract

BACKGROUND:

Cerebral cavernous malformations (CCM) present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members.

METHODS:

We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old) sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives.

RESULTS:

The phenotypes of cerebral cavernous malformations (CCMs) in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA.

CONCLUSIONS:

Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.

PMID:
12877753
PMCID:
PMC184376
DOI:
10.1186/1471-2377-3-5
[Indexed for MEDLINE]
Free PMC Article

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