Clinical and brain MRI follow-up study of a family with COL4A1 mutation

University of California, San Francisco, San Francisco, California, United States
Neurology (Impact Factor: 8.29). 11/2007; 69(16):1564-8. DOI: 10.1212/01.wnl.0000295994.46586.e7
Source: PubMed


To better delineate the clinical spectrum and the natural history of COL4A1 mutations, a newly defined genetic cause of small vessel disease including the brain and retina.
Clinical and brain MRI follow-up study of a family with COL4A1 mutation.
During a 7-year period, two affected members died from intracranial hemorrhage. Four other members had a COL4A1 mutation (age ranges 25 to 74 years). None reported stroke or retinal hemorrhage or hematuria and none had dementia according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Follow-up brain MRI showed grade 3 diffuse leukoencephalopathy in three out of four patients. All had dilated perivascular spaces and three out of four had silent microbleeds mainly in the deep white matter. MRI signal abnormalities did not change in severity, number, or location between baseline and follow-up imaging.
COL4A1 mutation carriers have great diversity in the clinical expression of the disease within the same family. Some affected family members may remain asymptomatic during several years of follow-up and have no evidence of progression of vascular changes on brain MRI.

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    • "E-mail: Article first published online in Wiley Online Library ( 00 Month 2014 DOI 10.1002/ajmg.a.36907 Ó 2015 Wiley Periodicals, Inc. et al., 2006; Sibon et al., 2007; Vahedi et al., 2007; Alamowitch et al., 2009; Bilguvar et al., 2009; De Vries et al., 2009, Shah et al., 2010; Livingston et al., 2011; Meuwissen et al., 2011; Tonduti et al., 2012; Lemmens et al., 2013] "
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    ABSTRACT: COL4A1 is located in humans on chromosome13q34 and it encodes the alpha 1 chain of type IV collagen, a component of basal membrane. It is expressed mainly in the brain, muscles, kidneys and eyes. Different COL4A1 mutations have been reported in many patients who present a very wide spectrum of clinical symptoms. They typically show a multisystemic phenotype. Here we report on the case of a patient carrying a novel de novo splicing mutation of COL4A1 associated with a distinctive clinical picture characterized by onset in infancy and an unusual evolution of the neuroradiological features. At three months of age, the child was diagnosed with a congenital cataract, while his brain MRI was normal. Over the following years, the patient developed focal epilepsy, mild diplegia, asymptomatic microhematuria, raised creatine kinase levels, MRI white matter abnormalities and brain calcification on CT. During the neuroradiological follow-up the extension and intensity of the brain lesions progressively decreased. The significance of a second variant in COL4A1 carried by the child and inherited from his father remains to be clarified. In conclusion, our patient shows new aspects of this collagenopathy and possibly a COL4A1 compound heterozygosity. © 2015 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 02/2015; 167(4). DOI:10.1002/ajmg.a.36907 · 2.16 Impact Factor
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    • "On retrouve e ´ galement des DEVR dans le cadre de certaines maladies neurologiques de mé canismes varié s. Elles seraient en effet retrouvé es chez 78 % de patients pré sentant une maladie de CADASIL (Cumurciuc et al., 2006) et e ´ galement identifié es chez des patients porteurs d'une mutation du gè ne COL4A1 (Vahedi et al., 2007). De mê me les DEVR sont observé es en IRM dans le cadre de certaines maladies mé taboliques, notamment l'adré noleucodystrophie (Groeschel et al., 2007), les mucopolysaccharidoses (Calleja Gero et al., 2012) (Matheus et al., 2004) et les mannosidoses (Patlas et al., 2001). "
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    ABSTRACT: Introduction Perivascular spaces, known as Virchow-Robin spaces (VRS), may become massively enlarged but are usually an incidental finding. However, a few reports on patients with unusually large VRS have mentioned association with neurological symptoms. We report a series of three symptomatic patients with extremely wide Virchow-Robin spaces documented on brain magnetic resonance imaging (MRI). Methods We retrospectively analyzed the medical records and brain MRI of three symptomatic patients, who had been diagnosed with VRS widening. Case reports In all three patients, the unusual widening of the VRS was located within the subcortical white matter with asymmetric distribution. Their neurological symptoms were epilepsy and neurological deficits which correlated well with the lesions seen on the MRI. Two patients had associated white matter hyperintensities: in the first case associated gliosis and in the second case, with vascular leukoencephalopathy. Conclusions Enlarged symptomatic VRS are rare. The underlying pathophysiological mechanisms remain uncertain. We report three cases with symptomatic giant dilatation of the Virchow-Robin spaces.
    Revue Neurologique 11/2013; 169(11):898–902. DOI:10.1016/j.neurol.2013.05.003 · 0.66 Impact Factor
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    • "These vascular defects may occur in isolation or be part of wider syndrome affecting the eye and kidneys (Plaisier et al. 2007; Sibon et al. 2007; Vahedi et al. 2007a). "
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    ABSTRACT: In 1990, the role of basement membranes in human disease was established by the identification of COL4A5 mutations in Alport's syndrome. Since then, the number of diseases caused by mutations in basement membrane components has steadily increased as has our understanding of the roles of basement membranes in organ development and function. However, many questions remain as to the molecular and cellular consequences of these mutations and the way in which they lead to the observed disease phenotypes. Despite this, exciting progress has recently been made with potential treatment options for some of these so far incurable diseases.
    Cell and Tissue Research 09/2009; 339(1):167-88. DOI:10.1007/s00441-009-0866-y · 3.57 Impact Factor
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