gms | German Medical Science

59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

01. - 04.06.2008, Würzburg

Identification of two novel mutations and of a novel critical region in the KRIT1 gene

Meeting Abstract

  • corresponding author V. Carotenuto - Neurosurgical Department, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy
  • D. Catapano - Neurosurgical Department, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy
  • V. Guarnieri - Medical Genetics Service, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy
  • L. A. Muscarella - Medical Genetics Service, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy
  • V. D’Angelo - Neurosurgical Department, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy
  • L. Zelante - Medical Genetics Service, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy
  • L. D’Agruma - Medical Genetics Service, “Casa Sollievo Sofferenza” Hospital and Scientific Research Institute, S. Giovanni Rotondo, Italy

Deutsche Gesellschaft für Neurochirurgie. Società Italiana di Neurochirurgia. 59. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 3. Joint Meeting mit der Italienischen Gesellschaft für Neurochirurgie (SINch). Würzburg, 01.-04.06.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. DocP 068

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2008/08dgnc336.shtml

Veröffentlicht: 30. Mai 2008

© 2008 Carotenuto et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective: Cerebral cavernous malformations (CCMs) represent a common autosomal dominant disorder that predisposes patients to hemorrhagic strokes and focal neurological signs. Mutations in three genes (KRIT1, MGC4607, and PDCD10) have been associated with CCMs. We investigated the role of two new mutations in the KRIT1 gene in two Italian families affected by CCMs.

Methods: Whole blood DNA was extracted and the mutations were detected after polymerase chain reaction (PCR), denaturing high-performance liquid chromatography screening, and sequencing of the coding regions of the three CCMs associated genes. Total RNA was extracted, and the KRIT1 cDNA was sequenced and subsequently subjected to realtime quantitative PCR in order to examine the translational outcome of each genomic mutation.

Results: A novel splicing acceptor site deletion of the exon 14 in one family and an intronic nucleotide change close to the exon 19 in the other one were identified, both in the KRIT1 gene. These mutations were proven to alter the correct splicing mechanism, resulting, respectively, in a truncated protein of 432 amino acids and in a protein lacking an internal segment.

Conclusions: We report two novel cases of splicing affecting genomic variants, suggesting a careful reanalysis of previously identified splice site variations in KRIT1 to look for their possible causative roles of similar missplicing events and their consequent involvement in the pathogenesis of CCMs. Moreover, our genotype-phenotype functional correlation suggests that the C-terminal portion of the KRIT1 protein is likely to contain a short, previously unrecognized segment necessary for its activity.