Document Detail

Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation.
MedLine Citation:
PMID:  18628313     Owner:  NLM     Status:  MEDLINE    
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.
V Laugel; C Dalloz; E S Tobias; J L Tolmie; D Martin-Coignard; V Drouin-Garraud; V Valayannopoulos; A Sarasin; H Dollfus
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Publication Detail:
Type:  Case Reports; Journal Article     Date:  2008-07-15
Journal Detail:
Title:  Journal of medical genetics     Volume:  45     ISSN:  1468-6244     ISO Abbreviation:  J. Med. Genet.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-02     Completed Date:  2008-09-24     Revised Date:  2013-02-12    
Medline Journal Info:
Nlm Unique ID:  2985087R     Medline TA:  J Med Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  564-71     Citation Subset:  IM    
Laboratory of Medical Genetics, Faculte de Medecine, 11 rue Humann, F-67000 Strasbourg, France.
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MeSH Terms
Amino Acid Sequence
Arthrogryposis / diagnosis*,  genetics,  pathology
Blotting, Western
Cataract / congenital*,  diagnosis,  genetics
Cell Survival
Cells, Cultured
DNA Helicases / analysis,  genetics*
DNA Mutational Analysis
DNA Repair
DNA Repair Enzymes / analysis,  genetics*
Genetic Complementation Test
Infant, Newborn
Microcephaly / diagnosis*,  genetics,  pathology
Molecular Sequence Data
Sequence Alignment
Reg. No./Substance:
EC 3.6.1.-/DNA Helicases; EC protein, human; EC 6.5.1.-/DNA Repair Enzymes

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