This blood vessel abnormality can cause episodes of bleeding within the eyes following any minor trauma to the eyes, leading to temporary vision loss. HANAC syndrome is caused by genetic changes in the COL4A1 gene. can also contribute. Jeanne M, Gould DB. Contact a health care provider if you have questions about your health. Role of COL4A1 in basement-membrane integrity and cerebral small-vessel disease. Oral expression was reduced and neuropsychological testing revealed language delay with a prominent expression deficit. To use the sharing features on this page, please enable JavaScript. So far, it appears as though mutations in COL4A1 and COL4A2 lead to identical disease, however, for reasons that are not yet understood, mutations in COL4A2 are much less frequent than those in COL4A1. COL4A1 mutations in patients with sporadic late-onset intracerebral The size and location of cerebral cavities contributes to clinical variability. Mutations in COL4A1 or COL4A2 cause Gould Syndrome and, because these two proteins are found in almost all tissues; nearly any organ can be affected. Therefore, it is important to note that there is a very broad spectrum of clinical presentations with different organs affected to different degrees between patients. (2005) 308:116771. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. Contact a health care provider if you have questions about your health. Epub 2022 Apr 14. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. Fetal origin of brain damage in 2 infants with a COL4A1 mutation: fetal and neonatal MRI. These genes are the blueprints for two proteins that wind together like a long rope inside cells. The disorder causes many symptoms, not the least of which are strokes and epilepsy. Arterial retinal tortuosity can cause episodes of bleeding within the eye following any minor trauma to the eye, leading to temporary vision loss. Phone: 202-588-5700. The COL4A2 test was negative. 2022 Sep;269(9):5153-5156. doi: 10.1007/s00415-022-11111-0. Only one copy of COL4A1 or COL4A2 needs to acquire a mutation in order to cause disease which means the mutations are Dominant thus, Gould Syndrome is considered Autosomal Dominant. We believe that the variant p.Gly743Val is likely pathogenic for several reasons. Clinical case reports suggest a syndrome with characteristic core findings; however, much about the disorder is not fully understood. COL4A1 mutations as a monogenic cause of cerebral 2015;84:918-926. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351667/, Meuwissen ME, Halley DJ, Smit LS, et al. The retina is the light-sensitive membrane that lines the inside of the eyes. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, et al. Many patients with COL4A1 and COL4A2 mutations have additional signs and symptoms that do not include the cerebral vasculature. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). Rannikme K, Davies G, Thomson PA, Bevan S, Devan WJ, Falcone GJ, et al. Copyright 2023 by Gould Syndrome Foundation -. Washington, DC 20036 cutting tissue called the corpus callosum, then make some additional delicate Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, Alamowitch S, Paques M, Ronco P. Am J Med Genet A. This variant highlights that the COL4A1 mutation should be sought in cases of familial ophthalmologic pathologies associated with congenital porencephaly or early onset leukoencephalopathy. Stay Informed With NORDs Email Newsletter, Launching Registries & Natural History Studies. MedlinePlus also links to health information from non-government Web sites. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature). Type IV collagen molecules attach to each other to form complex protein networks. If we dont have a program for you now, please continue to check back with us. MeSH COL4A2 mutation causing adult onset recurrent intracerebral hemorrhage and leukoencephalopathy. FOIA Lecordier S, Manrique-Castano D, El Moghrabi Y, ElAli A. COL4A1 Mutation in a Neonate With Intrauterine Stroke and Anterior Segment Dysgenesis. Before official website and that any information you provide is encrypted It is ubiquitously expressed in many tissues and cell types. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. 2010;41:e513-518. No patient had cramps, cardiac symptoms, or abnormalities or Raynaud phenomenon. doi: 10.1007/s00417-014-2800-6, 12. doi: 10.1212/01.WNL.0000123113.46672.68, 25. 13 and so Gould Syndrome is considered Autosomal and should affect males and females in equal numbers. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Cereb Circ Cogn Behav. Antiinflammatory therapy with canakinumab for atherosclerotic disease. COL4A1-related brain small-vessel disease is part of a group of conditions called the COL4A1-related disorders. (2010) 75:7479. (2014) 15:16. Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly. NORD is a registered 501(c)(3) charity organization. Ophthalmological features associated with COL4A1 mutations. The number of genes implicated in epilepsy has grown rapidly in the past decade. National Library of Medicine People with HANAC syndrome develop kidney disease (nephropathy). A novel COL4A1 gene mutation results in autosomal dominant non-syndromic congenital cataract in a Chinese family. Affected individuals have kidney disease (nephropathy) causing blood in the urine (hematuria) that can either be seen by the naked eye (gross hematuria) or only visible when tested (microscopic hematuria). 2017;155:45-57. https://www.ncbi.nlm.nih.gov/pubmed/28254515, Alavi MV, Mao M, Pawlikowski BT, et al. The COL4A1 gene mutations that cause COL4A1-related brain small-vessel disease result in the production of a protein that disrupts the structure of type IV collagen. MedlinePlus links to health information from the National Institutes of Health and other federal government agencies. We recently described hereditary angiopathy with nephropathy, aneurysm, and muscle cramps (HANAC) syndrome in 3 families with closely localized COL4A1 mutations. View CNBC interview with NORDs Peter Saltonstall and Boston Childrens Dr. Olaf Bodamer emphasizing the importance of investment in rare diseases. doi: 10.1007/s10897-008-9169-9, 16. INTERNET Zagaglia Selch C, Nisevic JR, et al. Gould Syndrome Foundation (COL4a1/COL4A2) - NORD (National Organization 2010 2022 Mar 24;3:100140. doi: 10.1016/j.cccb.2022.100140. Gould Syndrome is often characterized by abnormal blood vessels in the brain (cerebral vasculature defects), eye development defects (ocular dysgenesis), muscle disease (myopathy), and kidney abnormalities (renal pathology); however, many other aspects of the syndrome including abnormalities affecting the structure of the brain (cerebral cortical abnormalities) and lung (pulmonary) abnormalities continue to emerge and the full spectrum is still uncharacterized. Feb;24(1):63-8. doi: 10.1097/WCO.0b013e32834232c6. Arch Neurol. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. N Engl J Med. Rouaud T, Labauge P, Lasserve ET, Mine M, Coustans M, Deburghgraeve V, et al. Gould Syndrome - COL4A1 - COL4A2 genes - Gould Syndrome Foundation and transmitted securely. 2008 May;192(5):971-84; discussion 984-6. seizure activity. We describe, here, the phenotype of a likely pathologic variant (p.Gly743Val) in exon 30 of the COL4A1 gene, responsible for an oculo-cerebral phenotype characterized by severe hypermetropia and highly penetrant porencephaly in absence of other systemic complications. GeneReviews. Staals J, Makin SDJ, Doubal FN, Dennis MS, Wardlaw JM. By continuing to use this website, you agree to the Terms of Service & Privacy Policy, A Podcast For The Rare Disease Community, Policy Statements & Letters to Policymakers. HHS Vulnerability Disclosure, Help To date, over 50 pathogenic or likely pathogenic variants have been described in the COL4A1 gene, most of them missense (2). It affects mainly young adults, children and more typically neonates. Genet Med. At the age of 12, IV-3 underwent cerebral palsy quality of life (CPQoL) questionnaires in which they expressed a satisfactory quality of life and a good relationship with other children. Researchers are still trying to determine whether there are any specific genotype-phenotype correlations in COL4A1/A2-related disorders. COL4A1/A2-related disorders are caused by dominant mutations in the COL4A1 or COL4A2 genes. (18) and Staals et al. Developmental defects to the front of the eye, which also includes the ocular drainage structures between the iris and cornea, can lead to increased pressure in the eye (elevated intraocular pressure, or IOP). COL4A1 collagen type IV alpha 1 chain [ (human)] - National Center for In addition to the effects of a clear COL4A1 or COL4A2 mutation, large genetic studies reported associations for COL4A1/A2 with intracranial aneurysms, myocardial infarction, arterial calcification, arterial stiffness, deep intracerebral hemorrhages, lacunar ischemic stroke, reduced white matter volume and vascular leukoencephalopathy. When these ropes are secreted, they assemble into net-like structures outside the cells. She also showed severe hypermetropia. 55 Kenosia Avenue 2022 Oct 26;7(44):39680-39689. doi: 10.1021/acsomega.2c03360. We provide education, advocacy, and resources for families and individuals affected. Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, Marro B, National Institute of Neurological Disorders and Stroke. (2007) 357:268795. 2007 Aug;62(2):177-84. doi: 10.1002/ana.21191. Our data testing the effects of established mutations on collagen biosynthesis suggest that the intracellular retention of mutant COL4A1 proteins at the expense of their secretion appears to be a common effect of many COL4A1 mutations. Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity. Fax: 203-263-9938, Washington, DC Office However, in people with HANAC syndrome, these aneurysms typically do not burst. See our, COL4A1-related brain small-vessel disease, URL of this page: https://medlineplus.gov/genetics/condition/col4a1-related-brain-small-vessel-disease/. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Jeanne M, Gould DB. Clinical Testing and Workup A dashed arrow indicates secondary atrophy in the left cerebral peduncle. mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke. doi: 10.1111/cge.12543. Zeeva is one of fewer than 150 people in the world with a rare disease called Gould Syndrome or COL4A1/A2. How can gene variants affect health and development?
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