title: Manitoba aboriginal kindred with original cerebro-oculo- facio-skeletal syndrome has a mutation in the Cockayne syndrome group B (CSB) gene.
abstract: Cerebro-oculo-facio-skeletal (COFS) syndrome is a rapidly progressive neurological disorder leading to brain atrophy with calcification, cataracts, microcornea, optic atrophy, progressive joint contractures, and growth failure. Cockayne syndrome (CS) is a recessively inherited neurodegenerative disorder characterized by low-to-normal birth weight; growth failure; brain dysmyelination with calcium deposits; cutaneous photosensitivity; pigmentary retinopathy, cataracts, or both; and sensorineural hearing loss. CS cells are hypersensitive to UV radiation because of impaired nucleotide excision repair of UV radiation-induced damage in actively transcribed DNA. The abnormalities in CS are associated with mutations in the CSA or CSB genes. In this report, we present evidence that two probands related to the Manitoba Aboriginal population group within which COFS syndrome was originally reported have cellular phenotypes indistinguishable from those in CS cells. The identical mutation was detected in the CSB gene from both children with COFS syndrome and in both parents of one of the patients. This mutation was also detected in three other patients with COFS syndrome from the Manitoba Aboriginal population group. These results suggest that CS and COFS syndrome share a common pathogenesis.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Meira
authors.forename: J M
authors.initials: JM
authors.lastname: Graham
authors.forename: C R
authors.initials: CR
authors.lastname: Greenberg
authors.forename: D B
authors.initials: DB
authors.lastname: Busch
authors.forename: A T
authors.initials: AT
authors.lastname: Doughty
authors.forename: D W
authors.initials: DW
authors.lastname: Ziffer
authors.forename: D M
authors.initials: DM
authors.lastname: Coleman
authors.forename: I
authors.initials: I
authors.lastname: Savre-Train
authors.forename: E C
authors.initials: EC
authors.lastname: Friedberg
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D045643:DNA Repair Enzymes; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005816:Genetic Complementation Test; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008350:Manitoba; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors; D014429:Twins, Dizygotic / Q000235:genetics; D014466:Ultraviolet Rays
chemical_list: C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D014157:Transcription Factors; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes