title: Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation.
abstract: BACKGROUND
  The cerebro-oculo-facio-skeletal syndrome (COFS syndrome) is an autosomal recessive disorder which was initially described in a specific aboriginal population from 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.
authors.affiliation: Laboratory of Medical Genetics, Faculte de Medecine, 11 rue Humann, F-67000 Strasbourg, France. vincent.laugel@chru-strasbourg.fr
authors.forename: V
authors.initials: V
authors.lastname: Laugel
authors.forename: C
authors.initials: C
authors.lastname: Dalloz
authors.forename: E S
authors.initials: ES
authors.lastname: Tobias
authors.forename: J L
authors.initials: JL
authors.lastname: Tolmie
authors.forename: D
authors.initials: D
authors.lastname: Martin-Coignard
authors.forename: V
authors.initials: V
authors.lastname: Drouin-Garraud
authors.forename: V
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: A
authors.initials: A
authors.lastname: Sarasin
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
mesh_terms: D000595:Amino Acid Sequence; D001176:Arthrogryposis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D002386:Cataract / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000032:analysis / Q000235:genetics*; D019066:Facies; D005260:Female; D005816:Genetic Complementation Test; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008831:Microcephaly / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D008969:Molecular Sequence Data; D000075223:Poly-ADP-Ribose Binding Proteins; D016415:Sequence Alignment; D013577:Syndrome
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes