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Objective: To evaluate whether somatic mutations have role in saccular intracranial aneurysm pathogenesis Approach and Results: We performed whole exome sequencing of DNA derived from 20 saccular cerebral aneurysms followed by somatic variant calling. Eleven (55%) of the 20 patients had detectable nonsynonymous somatic mutations and in total, 48 mutations were detected in the aneurysm samples. The mutations were highly enriched in cancer-related genes and 37 were predictably deleterious. A p.Tyr562Asp somatic mutation was detected in the PDGFRB gene; somatic mutations at the same codon have been reported in fusiform cerebral aneurysms. Conclusions: These results widen the concept on the role of somatic mutations in cerebral aneurysms, indicating their possible role in the more common saccular aneurysm, similarly to the rarer fusiform aneurysm.

Neuromyelitis optica (NMO) is rare in Finland. To identify rare genetic variants contributing to NMO risk we performed whole exome, HLA and regulatory region sequencing in all ascertained cases during 2005-2013 (n=5) in a Southern Finnish population of 1.6 million. There were no rare variant shared by all patients. Four missense variants were shared by two patients in C3ORF20, PDZD2, C5ORF47 and ZNF606. Another PDZD2 variant was found in a third patient. In the non-coding sequence two predictably functional rare variants were shared by two patients. Our results do not support a homogeneous genetic etiology of NMO in Finland.