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Available from: Marisol E Otero, Nov 26, 2014
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    ABSTRACT: The term Ehlers-Danlos syndrome (EDS) encompasses a group of inherited connective tissue disorders. The manifestations of EDS can be seen in skin, joints, blood vessels and internal organs and vary from mild to severe and life threatening. Each subtype is a separate and different condition. The genetic basis of many subtypes has now been elucidated, confirming heterogeneity. An awareness of the different conditions within this group is the starting point towards accurate diagnosis. Accurate elicitation of history and clinical signs is vital in selecting the correct confirmatory investigation. Skin biopsy with electron microscopy can be helpful in the decision process of whether and when to perform genetic testing. Correct diagnosis within the EDSs allows targeted management, family screening and prenatal diagnosis.
    Archives of Disease in Childhood 07/2014; DOI:10.1136/archdischild-2013-304822 · 2.91 Impact Factor
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    ABSTRACT: The Ehlers-Danlos Syndromes comprise a heterogeneous group of diseases, which are characterized by fragility of the soft connective tissues and widespread manifestations in skin, ligaments and joints, blood vessels and internal organs. The clinical spectrum varies from mild skin and joint hyperlaxity to severe physical disability and life-threatening vascular complications. The current Villefranche classification recognizes six subtypes, most of which are linked to mutations in one of the genes encoding fibrillar collagen proteins or enzymes involved in post-translational modification of these proteins. Establishing the correct EDS subtype has important implications for genetic counselling and management and is supported by specific biochemical and molecular investigations. Over the last years, the characterisation of several new EDS variants has broadened insights into the molecular pathogenesis of EDS by implicating genetic defects in the biosynthesis of other extracellular matrix molecules, such as proteoglycans and tenascin-X, or genetic defects in molecules involved in intracellular trafficking, secretion and assembly of extracellular matrix proteins.
    Advances in Experimental Medicine and Biology 01/2014; 802:129-143. DOI:10.1007/978-94-007-7893-1_9 · 2.01 Impact Factor
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    ABSTRACT: Cryptic deletions in balanced de novo translocations represent a frequent cause of abnormal phenotypes, including Mendelian diseases. In this study, we describe a patient with multiple congenital abnormalities, such as late-onset congenital adrenal hyperplasia (CAH), primary ovarian failure and Ehlers-Danlos syndrome (EDS), who carries a de novo t(6;14)(p21;q32) translocation. Genomic array analysis identified a cryptic 1.1-Mb heterozygous deletion, adjacent to the breakpoint on chromosome 6, extending from 6p21.33 to 6p21.32 and affecting 85 genes, including CYP21A2,TNXB and MSH5. Multiplex ligation-dependent probe amplification analysis of the 6p21.3 region was performed in the patient and her family and revealed a 30-kb deletion in the patient's normal chromosome 6, inherited from her mother, resulting in homozygous loss of genes CYP21A1P and C4B. CYP21A2 sequencing showed that its promoter region was not affected by the 30-kb deletion, suggesting that the deletion of other regulatory sequences in the normal chromosome 6 caused a loss of function of the CYP21A2 gene. EDS and primary ovarian failure phenotypes could be explained by the loss of genes TNXB and MSH5, a finding that may contribute to the characterization of disease-causing genes. The detection of this de novo microdeletion drastically reduced the estimated recurrence risk for CAH in the family. © 2014 S. Karger AG, Basel.
    Sexual Development 06/2014; 8(4). DOI:10.1159/000363779 · 2.22 Impact Factor