Table 1

Systematic review of somatic variants in the pathogenesis of cerebral aneurysms

Study	Genes	No of patients	Aneurysm morphology	Molecular pathway	Therapeutic intervention
Hao et al (2024)8	PDGFRB	2	Fusiform	Promoted inflammatory related vascular smooth muscle cell phenotype and JAK-STAT pathway	Ruxolitinib, a JAK inhibitor, reversed the smooth muscle cell phenotype modulation in vitro and inhibited the vascular anomalies in zebrafish induced by PDGFRB mutation
Shima et al (2023)5	16 total somatic variants, 6 of which common to both ISA and IFA: PDGFRB, AHNAKi, OBSCN, CACNA1E, OR5P3, RNA binding motif protein 10 (RBM10)	65	Saccular (n=54), fusiform (n=11)	Four variants linked to the NFκB signaling pathway	Systemic administration of the TKI sunitinib blocked phenotype of fusiform-like dilatation of basilar artery in mutant PDGFRB mice
Lai et al (2022)7	SVIL	30	Saccular	Phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway	ROCK inhibitors
Li et al (2022)9	RNF213	174	N/A	Angiogenesis, vascular wall formation	N/A
Silverstein et al (2022)10	ANKRD17	1	N/A	Vascular wall formation/maintenance	N/A
Barak et al (2021)11	PPIL4	430	Saccular	PPIL4 potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator	N/A
Sauvigny et al (2020)12	EDIL3	38	N/A	Edil3 promotes adhesion of endothelial and vascular smooth muscle cells	N/A
Karasozen et al (2019)6	PDGFRB	1	Fusiform	Overactive autophosphorylation with downstream activation of ERK, SRC, and AKT	Non-ligand-dependent autophosphorylation inhibited by TKI sunitinib in fibroblast cells from index patient

IFA, intracranial fusiform aneurysm; ISA, intracranial saccular aneurysm; N/A, not available; NFκB, nuclear factor κB; TKI, tyrosine kinase inhibitor; vSMCs, vascular smooth muscle cells.