[Gene mutations in patients with hereditary cavernous malformations]

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Cerebral cavernous malformations (CCMs) are vascular abnormalities in the brain.
• Hereditary and sporadic forms of CCMs exist, with genetic mutations playing a key role.
• Understanding the genetic basis of CCMs is crucial for diagnosis and treatment.

Purpose of the Study:

• To identify mutations in cerebral cavernous malformation (CCM) genes within the Russian population.
• To investigate the prevalence of mutations in hereditary versus sporadic CCM cases.
• To correlate identified mutations with disease severity and clinical presentation.

Main Methods:

• Analysis of blood samples from 73 patients with confirmed or suspected CCMs.
• Multiplex ligation-dependent probe amplification (MLPA) used to detect large deletions/duplications in CCM genes.
• Whole genome sequencing performed on MLPA-negative samples to identify single nucleotide polymorphisms (SNPs).

Main Results:

• Mutations were detected in 91.7% of familial CCM cases.
• Deletions and SNPs in CCM1, CCM2, and CCM3 genes were identified in 27 patients.
• Patients with mutations exhibited greater disease severity, with CCM3 mutations linked to aggressive clinical courses.

Conclusions:

• The distribution of mutations in known CCM genes aligns with previous large-scale studies.
• Familial CCMs are associated with a more severe disease progression.
• The findings suggest that genetic mutations beyond currently known CCM genes may contribute to familial CCMs.