Article Text

other Versions

Download PDFPDF
COFS syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation.
  1. Vincent Laugel (vincent.laugel{at}chru-strasbourg.fr)
  1. Laboratory of Medical Genetics, Faculte de Medecine de Strasbourg, France
    1. Cecile Dalloz
    1. Laboratory of Medical Genetics, Faculte de Medecine de Strasbourg, France
      1. Edward S Tobias
      1. Division of Developmental Medicine, the Royal Hospital for Sick Children, University of Glasgow, United Kingdom
        1. John L Tolmie
        1. Division of Developmental Medicine, the Royal Hospital for Sick Children, University of Glasgow, United Kingdom
          1. Dominique Martin-Coignard
          1. Department of Medical Genetics, University Hospital, Le Mans, France
            1. Valerie Drouin-Garraud
            1. Department of Medical Genetics, University Hospital, Rouen, France
              1. Vassili Valayannopoulos
              1. Department of Metabolic Disorders, Necker Hospital, Paris, France
                1. Alain Sarasin
                1. FRE2939, Institut Gustave Roussy, Villejuif, France
                  1. Helene Dollfus
                  1. Laboratory of Medical Genetics, Faculte de Medecine de Strasbourg, France

                    Abstract

                    Background: The cerebro-oculo-facio-skeletal syndrome (COFS syndrome) is an autosomal recessive disorder which was initially described in a specific aboriginal population of Manitoba. In recent years, COFS syndrome has been linked in this original population to a defective DNA repair pathway and to a homozygous mutation in the major gene underlying Cockayne syndrome (CSB). However, most reports of suspected COFS syndrome outside this population have not been confirmed at the molecular level, leading to considerable heterogeneity within the syndrome and confusing overlaps between COFS syndrome and other eye and brain disorders.

                    Objective: To refine the delineation of the syndrome on genetically proven COFS cases. Methods: We report the exhaustive clinical, cellular and molecular data of three unrelated COFS patients with mutations in the CSB gene.

                    Results: All three patients present the cardinal features of COFS syndrome including extreme microcephaly, congenital cataracts, facial dysmorphism and arthrogryposis. They also exhibit a predominantly postnatal growth failure, a severe psychomotor retardation, with axial hypotonia and peripheral hypertonia and neonatal feeding difficulties. Fibroblasts from the patients show the same DNA repair defect which can be complemented by transfection of the CSB wild-type cDNA. Five new mutations in the CSB gene have been identified in these patients.

                    Conclusions: Our data indicate that COFS syndrome represents the most severe end of the Cockayne spectrum. New diagnostic criteria for COFS syndrome are proposed, based on our findings and on the few genetically proven COFS cases from the literature.

                    Statistics from Altmetric.com

                    Request Permissions

                    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.