CCM2 gene polymorphisms in Italian sporadic patients with cerebral cavernous malformation: A case-control study

Rosalia D'Angelo, Concetta Scimone, Carmela Rinaldi, Giuseppe Trimarchi, Domenico Italiano, Placido Bramanti, Aldo Amato, Antonina Sidoti

Research output: Contribution to journalArticlepeer-review


Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities that can occur sporadically or as a familial autosomal dominant condition with incomplete penetrance and variable clinical expression attributable to mutations in three different genes: CCM1 (Krit1), CCM2 (MGC4607) and CCM3 (PDCD10). Among our group of CCM Italian patients, we selected a cohort of sporadic cases negative for mutations in CCM genes. In this cohort, five variants in CCM2 gene were detected, which proved to be the known polymorphisms in intronic regions (IVS2-36A>G and IVS8 +119 C>T) and in coding sequence (c.157 G>A in exon 2, c.358 G>A in exon 4 and c.915 G>A in exon 8). Therefore, we undertook a case-control study to investigate the possible association of these polymorphisms with sporadic CCMs. The five polymorphisms were identified in 91 CCM sporadic patients and in 100 healthy controls by direct sequencing methods using lymphocyte DNA. Polymorphisms IVS2-36A>G and c.915 G>A showed statistically significant differences in frequencies between patients and controls [(χ 2, 6.583; P2, 14.205; PG) had a significant increase for CCM risk (OR, 3.08; 95% CI, 1.5-5.9 and OR, 4.3; 95% CI, 1.4-22.6) and the same was observed for the polymorphism c.915 G> A (genotype G/A OR, 6.1; 95% CI, 3.0-12.6 and genotype A/A OR, 2.79). In addition, the polymorphisms c.358 G>A in exon 4 (χ 2, 15.977; PA in exon 8 (χ 2, 18.109; PA (p.Val120Ile), c.915 G>A (p.Thr305 Thr) and IVS2-36A>G, shows that haplotype GAG (+--) significantly increased among CCM sporadic patients compared to the control group. Significant differences between patients and controls were observed only for IVS2-36A>G and c.915 G>A polymorphisms indicating their possible association with sporadic CCMs and an increased risk of CCM. On the other hand, polymorphisms c.358 G>A and c.915 G>A were associated with a more benign course of the disease. These data were confirmed by the haplotype GAG (+--) frequencies.

Original languageEnglish
Pages (from-to)1113-1120
Number of pages8
JournalInternational Journal of Molecular Medicine
Issue number6
Publication statusPublished - Jun 2012


  • CCM2 polymorphisms and symptoms
  • Cerebral cavernous malformations and risk
  • Genetic screening in italian population
  • Haplotype distribution

ASJC Scopus subject areas

  • Genetics


Dive into the research topics of 'CCM2 gene polymorphisms in Italian sporadic patients with cerebral cavernous malformation: A case-control study'. Together they form a unique fingerprint.

Cite this