TABLE 1: CEREBROVASCULAR DISEASES AND ASSOCIATED GENES.

List of diseases, associated genes with chromosomal localization, pattern of inheritance, function of encoded proteins, and main references are given. AD: autosomal dominant. APP: amyloid precursor protein. AR: autosomal recessive. BRCC3: BRCA1/BRCA2-containing complex subunit 3. BRI2: integral membrane protein 2B. CAA: cerebral amyloid angiopathy. CADASIL: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. CARASIL: cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. CCM: cerebral cavernous malformations. CDKN2A-B: cyclin-dependent kinase inhibitor 2A-B. CNNM2: cyclin M2. CRV: cerebroretinal vasculopathy. CST3: cystatin C. EDNRA: endothelin receptor type A. GSN: gelsolin. GUCY1A3: guanylate cyclase soluble subunit alpha-3. HTRA1: high-temperature requirement A serine peptidase 1. IA: intracranial aneurysms. KL/STARD13: Klotho/StAR related lipid transfer domain containing 13. KRIT1: Krev1 interaction trapped gene 1. MMD: Moyamoya disease. NOTCH3: neurogenic locus notch homolog protein 3. PDCD10: programmed cell death protein 10. RBBP8: retinoblastoma binding protein 8. RNF213: ring finger protein 213. SOX17: SRY-related HMG-box family member 17. TTR: transthyretin. TREX1: three prime repair exonuclease 1. XR: X-linked recessive.

Disease	Gene	Chromosome	Inheritance	Function	Reference
Hemorrhagic Disease
	CCM1/KRIT1	7q	AD	controlling endothelial barrier junctions	Laberge-le Couteulx et al., 1999 [44]
CCM	CCM2	7p	AD	controlling endothelial barrier junctions	Liquori et al., 2003 [45] Denier et al., 2004 [46]
	CCM3/PDCD10	3q	AD	induction of apoptosis; broadly expressed	Bergametti et al., 2005 [47] Guclu et al., 2005 [48]
	SOX17	8q	-	maintenance of arterial integrity	Bilguvar et al., 2008 [139] Yasuno et al., 2010 [140]
	CDKN2A-B	9p	-	cell growth regulator	Bilguvar et al., 2008 [139] Yasuno et al., 2010 [140] Leeper et al., 2013 [145]
IA	CNNM2	10q	-	unknown	Yasuno et al., 2010 [140]
	KL/STARD13	13q	-	unknown/cell proliferation	Yasuno et al., 2010[140]
	RBBP8	18q	-	cell cycle progression	Yasuno et al., 2010 [140]
	EDNRA	4q	-	vasoconstriction	Yasuno et al., 2011 [141]
	RNF213	17q	AD	angiogenic response to inflammation	Kamada et al., 2011 [159] Liu et al., 2011 [160]
MMD	GUCY1A3	4q	AR	subunit of the major NO-receptor in the vascular wall	Herve et al., 2014 [169]
	BRCC3	Xq	XR	proper angiogenesis	Miskinyte et al., 2011 [170]
Small Vessel Disease
CADASIL	NOTCH3	19q	AD	cell fate; stability of vascular smooth muscle cells	Joutel et al., 1996 [182]
CARASIL	HTRA1	10q	AR	serine protease; regulation of TGFβ signaling	Hara et al., 2009 [183]
	APP	21q	AD	multiple; primary function unknown	Rovelet-Lecrux et al., 2006 [245]
	BRI2	13q	AD	unknown	Vidal et al., 1999 [253]
CAA	CST3	20p	AD	cysteine protease inhibitor	Ghiso et al., 1986 [249]
	TTR	18q	AD	transportation of thyroxine and retinol-binding protein	Brett et al., 1999 [250]
	GSN	9q	AD	actin filament dynamics	Ghiso et al., 1990 [251]
CRV	TREX1	3p	AD	maintenance of vascular integrity	Richards et al., 2007 [184]