MLPA-анализ генов ССМ у больных с различными формами кавернозных мальформаций ЦНС в российской популяции

Abstract

Mutations in the CCM genes causing the formation of cavernous malformations (СМ) are being actively studied and their list is constantly growing. Mutations in the CCM genes are usually analyzed using two main approaches: multiplex ligation-dependent probe amplification (MLPA) - to search for large deletions/insertions and exon sequencing - to search for mutations leading to amino acid substitutions, the appearance of premature translation termination, reading frame shifts and splice site junction. On the basis of these data, cheaper diagnostic test systems are created that allow the identification of mutant alleles in order to predict the possible occurrence and development of cerebral cavities. Objective. Identification of large deletions in CCM genes associated with the developing of cerebral СМ in patients with sporadic and hereditary forms of the disease in the Russian population. Methods. Blood samples from 92 selected patients were examined, among them - 45 with a hereditary form of the disease, 2 - with clinically confirmed familial cases and 45 - so-called sporadic cases, as well as in 10 healthy relatives. Presence of large deletions/duplications was detected by multiplex ligation-dependent probe amplification (MPLA). Results. Major rearrangements in one of the CCM genes ( CCM1 , CCM2 , CCM3 ) were identified in 10 samples, including 2 patients with conditionally familial form of CM, and 3 patients with a sporadic form. Of the seven types of mutations identified, four were not previously described. Two deletions in the CCM3 [PDCD10] gene were identified, for which such mutations have not yet been described. The ratio of mutations in the CCM1 , CCM2 and CCM3 genes was 40%, 30% and 30%, respectively. The most aggressive clinical course was observed in patients with mutations in the CCM3 gene. Conclusion. The analysis showed that large deletions in the genes of CCM are quite common in patients with sporadic and hereditary forms of the disease in the Russian population and accounted for approximately 11% of the studied sample. At the same time, new types of mutations that are not described in other populations have been identified