Research & Literature

The expanding phenotype of COL4A1 and COL4A2 mutations: clinical data on 13 newly identified families and a review of the literature.

Meuwissen ME, Halley DJ, Smit LS, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2015; (17(11)):843-53 doi:10.1038/gim.2014.210.

Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention.

Jeanne M, Jorgensen J, Gould DB

Circulation 2015; (131(18)):1555-65 doi:10.1161/CIRCULATIONAHA.114.013395.

Two families with novel missense mutations in COL4A1: When diagnosis can be missed.

Giorgio E, Vaula G, Bosco G, et al.

Journal of the neurological sciences 2015; (352(1-2)):99-104.

HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease.

Chen Z, Migeon T, Verpont MC, et al.

Journal of the American Society of Nephrology : JASN 2016; (27(4)):1042-54 doi:10.1681/ASN.2014121217.

A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen.

Gale DP, Oygar DD, Lin F, et al.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2016; (31(11)):1908-1914 doi:10.1093/ndt/gfw051.

Disruption of a miR-29 binding site leading to COL4A1 upregulation causes pontine autosomal dominant microangiopathy with leukoencephalopathy.

Verdura E, Hervé D, Bergametti F, et al.

Annals of neurology 2016; (80(5)):741-753 doi:10.1002/ana.24782.

HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect.

Guiraud S, Migeon T, Ferry A, et al.

The American journal of pathology 2017; (187(3)):505-516 doi:10.1016/j.ajpath.2016.10.020.

Hereditary cerebral small vessel disease and stroke.

Søndergaard CB, Nielsen JE, Hansen CK, Christensen H

Clinical neurology and neurosurgery 2017; (155()):45-57 doi:10.1016/j.clineuro.2017.02.015.

Long-Term Prognostic Implications of Cerebral Microbleeds in Chinese Patients With Ischemic Stroke.

Lau KK, Wong YK, Teo KC, et al.

Journal of the American Heart Association 2017; (6(12)) doi:10.1161/JAHA.117.007360.

Severity of arterial defects in the retina correlates with the burden of intracerebral haemorrhage in COL4A1-related stroke.

Ratelade J, Mezouar N, Domenga-Denier V, et al.

The Journal of pathology 2018; (244(4)):408-420 doi:10.1002/path.5023.

Updates on Prevention of Hemorrhagic and Lacunar Strokes.

Tsai HH, Kim JS, Jouvent E, Gurol ME

Journal of stroke 2018; (20(2)):167-179 doi:10.5853/jos.2018.00787.

Use of sodium 4-phenylbutyrate to define therapeutic parameters for reducing intracerebral hemorrhage and myopathy in Col4a1 mutant mice.

Hayashi G, Labelle-Dumais C, Gould DB

Disease models & mechanisms 2018; (11(7)) doi:10.1242/dmm.034157.

Neurologic phenotypes associated with COL4A1/2 mutations: Expanding the spectrum of disease.

Zagaglia S, Selch C, Nisevic JR, et al.

Neurology 2018; (91(22)):e2078-e2088 doi:10.1212/WNL.0000000000006567.

COL4A1 Mutations Cause Neuromuscular Disease with Tissue-Specific Mechanistic Heterogeneity.

Labelle-Dumais C, Schuitema V, Hayashi G, et al.

American journal of human genetics 2019; (104(5)):847-860 doi:10.1016/j.ajhg.2019.03.007.

Antiplatelet Therapy in Cerebral Small Vessel Disease.

Bouasquevisque DS, Benavente OR, Shoamanesh A

Current neurology and neuroscience reports 2019; (19(9)):61 doi:10.1007/s11910-019-0979-y.

A Case of Leukoencephalopathy and Small Vessels Disease Caused by a Novel HTRA1 Homozygous Mutation.

Gündüz T, Demirkol Y, Doğan Ö, et al.

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2019; (28(11)):104354 doi:10.1016/j.jstrokecerebrovasdis.2019.104354.

Reducing Hypermuscularization of the Transitional Segment Between Arterioles and Capillaries Protects Against Spontaneous Intracerebral Hemorrhage.

Ratelade J, Klug NR, Lombardi D, et al.

Circulation 2020; (141(25)):2078-2094 doi:10.1161/CIRCULATIONAHA.119.040963.

Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology.

Mancuso M, Arnold M, Bersano A, et al.

European journal of neurology 2020; (27(6)):909-927 doi:10.1111/ene.14183.

Beyond the Brain: Systematic Review of Extracerebral Phenotypes Associated With Monogenic Cerebral Small Vessel Disease.

Rannikmäe K, Henshall DE, Thrippleton S, et al.

Stroke 2020; (51(10)):3007-3017 doi:10.1161/STROKEAHA.120.029517.

Assessing the utility of long-read nanopore sequencing for rapid and efficient characterization of mobile element insertions.

Watson CM, Crinnion LA, Lindsay H, et al.

Laboratory investigation; a journal of technical methods and pathology 2021; (101(4)):442-449.

Recurrent Pontine Strokes in a Young Male.

Grobe-Einsler M, Urbach H, Paus S

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2020; (29(12)):105386 doi:10.1016/j.jstrokecerebrovasdis.2020.105386.

Relation between physical activity and cerebral small vessel disease: A nine-year prospective cohort study.

Landman TR, Thijssen DH, Tuladhar AM, de Leeuw FE

International journal of stroke : official journal of the International Stroke Society 2021; (16(8)):962-971 doi:10.1177/1747493020984090.

In Silico identification of a common mobile element insertion in exon 4 of RP1.

Won D, Hwang JY, Shim Y, et al.

Scientific reports 2021; (11(1)):13381 doi:10.1038/s41598-021-92834-4.

ESO Guideline on covert cerebral small vessel disease.

Wardlaw JM, Debette S, Jokinen H, et al.

European stroke journal 2021; (6(2)):CXI-CLXII doi:10.1177/23969873211012132.

A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy.

Li Q, Wang C, Li W, et al.

Translational stroke research 2022; (13(2)):238-244 doi:10.1007/s12975-021-00926-0.

Identification of fibronectin 1 as a candidate genetic modifier in a Col4a1 mutant mouse model of Gould syndrome.

Mao M, Popli T, Jeanne M, et al.

Disease models & mechanisms 2021; (14(4)) doi:10.1242/dmm.048231.

Epilepsy and related challenges in children with COL4A1 and COL4A2 mutations: A Gould syndrome patient registry.

Boyce D, McGee S, Shank L, et al.

Epilepsy & behavior : E&B 2021; (125()):108365 doi:10.1016/j.yebeh.2021.108365.

2021 Taiwan Stroke Society Guidelines of blood pressure control for ischemic stroke prevention.

Chi NF, Chung CP, Cheng HM, et al.

Journal of the Chinese Medical Association : JCMA 2022; (85(6)):651-664 doi:10.1097/JCMA.0000000000000738.

Main features of COL4A1-COL4A2 related cerebral microangiopathies.

Guey S, Hervé D

Cerebral circulation - cognition and behavior 2022; (3()):100140 doi:10.1016/j.cccb.2022.100140.

Non-convulsive status epilepticus as the initial manifestation in a family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

González F, Bala M, Saucedo M, et al.

Neurologia 2023; (38(2)):82-86 doi:10.1016/j.nrleng.2020.04.031.

Elevated TGFβ signaling contributes to cerebral small vessel disease in mouse models of Gould syndrome.

Branyan K, Labelle-Dumais C, Wang X, et al.

Matrix biology : journal of the International Society for Matrix Biology 2023; (115()):48-70 doi:10.1016/j.matbio.2022.11.007.

Genetic Causes of Cerebral Small Vessel Diseases: A Practical Guide for Neurologists.

Manini A, Pantoni L

Neurology 2023; (100(16)):766-783 doi:10.1212/WNL.0000000000201720.

Pontine autosomal dominant microangiopathy with leukoencephalopathy: Col4A1 gene variants in the original family and sporadic stroke.

Roos J, Müller S, Giese A, et al.

Journal of neurology 2023; (270(5)):2631-2639 doi:10.1007/s00415-023-11590-9.

PI3K block restores age-dependent neurovascular coupling defects associated with cerebral small vessel disease.

Thakore P, Yamasaki E, Ali S, et al.

bioRxiv : the preprint server for biology 2023; doi:10.1101/2023.03.03.531032.

Diagnosis and Management of Cerebral Small Vessel Disease.

Sharrief A

Continuum (Minneapolis, Minn.) 2023; (29(2)):501-518 doi:10.1212/CON.0000000000001232.

Venous Tortuosity in COL4A2-Associated Gould Syndrome.

Oh JK, Levi SR, de Carvalho JRL, et al.

Ophthalmic surgery, lasers & imaging retina 2023; (54(9)):536-539 doi:10.3928/23258160-20230811-01.

Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples.

Wijngaard R, Demidov G, O'Gorman L, et al.

European journal of human genetics : EJHG 2024; (32(2)):200-208 doi:10.1038/s41431-023-01478-7.

'Raisin bread sign' feature of pontine autosomal dominant microangiopathy and leukoencephalopathy.

Kikumoto M, Kurashige T, Ohshita T, et al.

Brain communications 2023; (5(6)):fcad281 doi:10.1093/braincomms/fcad281.

Cardiovascular Management in Asymptomatic (Silent) Cerebral Microbleeds and Suspected Cerebral Amyloid Angiopathy.

Charidimou A, Smith EE

Stroke 2024; (55(4)):1101-1112 doi:10.1161/STROKEAHA.123.044167.

Small-vessel disease in the brain.

Singh A, Bonnell G, De Prey J, et al.

American heart journal plus : cardiology research and practice 2023; (27()):100277 doi:10.1016/j.ahjo.2023.100277.

An AluYa5 Insertion in the 3'UTR of COL4A1 and Cerebral Small Vessel Disease.

Aloui C, Neumann L, Bergametti F, et al.

JAMA network open 2024; (7(4)):e247034 doi:10.1001/jamanetworkopen.2024.7034.

Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene.

Fernández-Suárez E, González-Del Pozo M, Méndez-Vidal C, et al.

Mobile DNA 2024; (15(1)):9 doi:10.1186/s13100-024-00320-1.

Evaluating neural crest cell migration in a Col4a1 mutant mouse model of ocular anterior segment dysgenesis.

Cozzitorto C, Peltz Z, Flores LM, et al.

Cells & development 2024; (179()):203926 doi:10.1016/j.cdev.2024.203926.

Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol.

Gasparini S, Balestrini S, Saccaro LF, et al.

American journal of medical genetics. Part C, Seminars in medical genetics 2024; (196(4)):e32099 doi:10.1002/ajmg.c.32099.

Clinical Reasoning: A 50-Year-Old Man With Intracerebral Hemorrhage and Tortuous Retinal Arterioles.

Bouchart J, Weber S, Coste T, et al.

Neurology 2024; (103(6)):e209796 doi:10.1212/WNL.0000000000209796.

Monogenic causes of cerebral small vessel disease and stroke.

Guey S, Chabriat H

Handbook of clinical neurology 2024; (204()):273-287 doi:10.1016/B978-0-323-99209-1.00018-1.

COL4A2 -Related Disorder Presenting in Adulthood With Rhabdomyolysis.

Olarewaju BA, Tejon J, Shurrab S, et al.

American journal of medical genetics. Part A 2025; (197(4)):e63965 doi:10.1002/ajmg.a.63965.

Identity-by-Descent Analysis Uncovering a Founder Event in a Novel Hereditary Small Vessel Cerebral Disease.

Maillard A, Pipiras E, Jarnoux P, et al.

Stroke 2025; (56(5)):1285-1289 doi:10.1161/STROKEAHA.124.049839.

COL4A1 and COL4A2-related disorders: Clinical features, diagnostic guidelines, and management.

Tambala D, Vassar R, Snow J, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2025; (27(9)):101514 doi:10.1016/j.gim.2025.101514.

More than lacunes and leukoencephalopathy: A hemorrhagic stroke in CADASIL.

Jabbari C, Laridi A, Laasri I, et al.

Radiology case reports 2025; (20(9)):4873-4876 doi:10.1016/j.radcr.2025.06.037.

Rapid genetic testing in the PICU: uncovering COL4A2-related GOULD syndrome in super-refractory status epilepticus.

Sporn KC, Garg R, Sakonju A

BMJ case reports 2025; (18(7)) doi:10.1136/bcr-2025-266705.

Zebrafish col4a1 loss-of-function models mirror key neurovascular and ocular features of COL4A1/A2 syndrome and enable human variants assessment in vivo.

Paradisi G, Bonavolontà V, Venditti M, et al.

Matrix biology : journal of the International Society for Matrix Biology 2026; (143()):63-82 doi:10.1016/j.matbio.2025.11.004.

Limitations of short-read NGS in detecting RP1 Alu insertions: a case emphasizing Sanger confirmation.

Hayashi T, Mizobuchi K, Higa N, et al.

Ophthalmic genetics 2026; (47(2)):204-208 doi:10.1080/13816810.2025.2590162.

Multimodal neuroimaging of Col4a1-mutant mouse models of Gould syndrome.

Gao X, Wang X, Labelle-Dumais C, et al.

Frontiers in neuroscience 2025; (19()):1639871 doi:10.3389/fnins.2025.1639871.

Late-onset intracerebral hemorrhage associated with COL4A1 variants: clinical and genetic perspectives.

Zhuang X, Xu S, Chen C, et al.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2026; (47(1)):97.

Fusiform dilatation of the ascending aorta and outpouching of the left A2 anterior cerebral artery segment in COL4A1 -related disorder.

Olarewaju BA, Tejon JB, Bcharah G, et al.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 2026; (47(1)):138.

Stratification of Phenotypes in Childhood-Onset COL4A1/COL4A2-Related Disorders Based on Age of Presentation.

Porcari GS, Rashid RN, Mulvihill CA, et al.

Neurology. Genetics 2026; (12(3)):e200386 doi:10.1212/NXG.0000000000200386.

A novel mouse model of cerebral microbleeds by targeted Col4a1 editing in adult brain microvessels.

Kim H, Seo Y, Kho H, et al.

Brain : a journal of neurology 2026; (149(10)):3566-3581 doi:10.1093/brain/awag048.

Recent developments and challenges in hypertensive dementia over the past year.

Mogi M, Hoshide S, Kario K

Hypertension research : official journal of the Japanese Society of Hypertension 2026; (49(8)):2301-2306 doi:10.1038/s41440-026-02714-5.

Pontine autosomal dominant microangiopathy with leukoencephalopathy in a Hispanic man without a family history.

Shah A, Hussain U, Ekpruke C, et al.

Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association 2026; (35(9)):108700 doi:10.1016/j.jstrokecerebrovasdis.2026.108700.

Long-Term Clinical Course of COL4A1-Associated Nephropathy and Assessment of α1 Chain of Type IV Collagen Expression in Kidney Biopsy Specimens: A Case Report.

Yoshida R, Hashiguchi A, Nakayama T, et al.

American journal of kidney diseases : the official journal of the National Kidney Foundation 2026; (88(4)):631-635 doi:10.1053/j.ajkd.2026.05.014.

The Expanding Phenotypic Spectrum of COL4A1- and COL4A2-Related Disorders: A Systematic Review.

Bonaventura E, Marelli D, Carugo U, et al.

Pediatric neurology 2026; (183()):10-21 doi:10.1016/j.pediatrneurol.2026.06.025.