COL4A1 mutation in Axenfeld-Rieger anomaly with leukoencephalopathy and stroke
ABSTRACT Several hereditary ischemic small-vessel diseases of the brain have been reported during the last decade. Some of them have ophthalmological, mainly retinal, manifestations. Herein, we report on a family affected by vascular leukoencephalopathy and variable abnormalities of the anterior chamber of the eye.
After the occurrence of a small, deep infarct associated with white matter lesions in a patient with a medical history of congenital cataract and amblyopia, we conducted clinical and neuroradiological investigations in 10 of her relatives.
Diffuse leukoencephalopathy associated with ocular malformations of the Axenfeld-Rieger type was observed in five individuals. Familial genetic analyses led to the identification of a novel missense mutation in the COL4A1 gene, p.G720D, which cosegregates with the disease.
Our data corroborate previous observations demonstrating the role of COL4A1 in cerebral microangiopathy and expand the phenotypic spectrum associated with mutations in this gene. We delineate a novel association between the Axenfeld-Rieger anomaly and leukoencephalopathy and stroke. Ann Neurol 2007.
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- "E-mail: firstname.lastname@example.org Article first published online in Wiley Online Library (wileyonlinelibrary.com): 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] "
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 · 2.05 Impact Factor
- "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). "
Article: Basement membranes and human disease[Show abstract] [Hide abstract]
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 · 3.33 Impact Factor
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ABSTRACT: Current industrial processes are characterized by encompassing a large number of interdependent variables, which very often exhibit autocorrelated behavior, due to the dynamic nature of the phenomena involved, associated with the high sampling rates of modern data acquisition systems. Multivariate statistical process control charts have been developed to handle the cross-correlation issue, such as the Hotelling's T2, MEWMA and MCUSUM control charts, but they are not able to handle properly the presence of autocorrelation in data. In order to address both problems simultaneously, alternative procedures were developed, namely by adapting the control limits, using residuals from time series modeling and applying data transformation techniques, some of which will be addressed in this paper, along with others we now propose. The proposed monitoring methods use a combination of Dynamic PCA (DPCA), ARMA models and missing data estimation methods, allowing for the simultaneous reduction of data dimensionality while capturing its dynamic behavior, therefore also handling the autocorrelation effects.The results obtained show that the proposed methodologies based upon missing data estimation tend to present better performance, constituting good alternatives to methodologies currently in use.